Molecule Information

General Information of the Molecule (ID: Mol00372)

• Name: Fibroblast growth factor receptor 2 (FGFR2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: FGFR2
• Gene ID: 2263
• Location: chr10:121478332-121598458[-]
• Sequence:
  MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEV
  RCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYF
  MVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCP
  AGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSI
  NHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSK
  YGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVL
  PAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTK
  RIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDK
  LTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKM
  IGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTF
  KDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKT
  TNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGH
  RMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYS
  PSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT
• Function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.
• Uniprot ID: FGFR2_HUMAN
• Ensembl ID: ENSG00000066468
• HGNC ID: HGNC:3689

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Infigratinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [1]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.V564F (c.1690G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V564F (c.1690G>T) in gene FGFR2 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Duplication; p.S267_D273 (c.799_819)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Infigratinib
• Molecule Alteration: Complex-indel; p.W290_I291delinsC (c.870_872delGAT)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay

Lapatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [4]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Lapatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: YCC1 cells; Gastric; Homo sapiens (Human); CVCL_9646
• In Vitro Model: YCC1-F cells; Gastric; Homo sapiens (Human); CVCL_9646
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR 494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2 positive gastric cancer.

Lenvatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Lenvatinib
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Lenvatinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Lenvatinib
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Lenvatinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Lenvatinib
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Lenvatinib by aberration of the drug's therapeutic target

Pemigatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Hepatocellular carcinoma [5]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Pemigatinib
• Molecule Alteration: Function; Inhibition
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genomic profiling assay
• Mechanism Description: The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with FGFR2. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Pemigatinib is a selective, potent, oral, competitive inhibitor of FGFR1, 2, and 3 that inhibits receptor autophosphorylation and subsequent activation of FGF/FGFR-mediated signaling networks, leading to an inhibition of tumor cell growth in FGFR-driven cancers.

Clinical Trial Drug(s) 8 drug(s) in total

Brivanib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [6]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: Brivanib
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Brivanib by unusual activation of pro-survival pathway

Cediranib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Cediranib
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Cediranib
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Disease Class: Endometrial adenocarcinoma [6]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: Cediranib
• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.N549K (c.1647T>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway

Disease Class: Endometrial adenocarcinoma [6]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: Cediranib
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Cediranib
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Derazantinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [7]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: Derazantinib
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: SW780 cells; Bladder; Homo sapiens (Human); CVCL_1728
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: RT-112 cells; Urinary bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: MFM-223 cells; Pleural effusion; Homo sapiens (Human); CVCL_1408
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: COS-1 cells; Kidney; Chlorocebus aethiops (Green monkey); CVCL_0223
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.

Disease Class: Endometrial adenocarcinoma [7]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: Derazantinib
• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: SW780 cells; Bladder; Homo sapiens (Human); CVCL_1728
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: RT-112 cells; Urinary bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: MFM-223 cells; Pleural effusion; Homo sapiens (Human); CVCL_1408
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: COS-1 cells; Kidney; Chlorocebus aethiops (Green monkey); CVCL_0223
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.

Selumetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [8]

• Resistant Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: SUM-52PE cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: NCI-H1581 cells; Lung; Homo sapiens (Human); CVCL_1479
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: KMS-11 cells; Pleural effusion; Homo sapiens (Human); CVCL_2989
• In Vitro Model: HSC-39 cells; Ascites; Homo sapiens (Human); CVCL_A385
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: KATO-III cells; Pleural effusion; Homo sapiens (Human); CVCL_0371
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• Experiment for Molecule Alteration: Microarray assay; Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

AZD-4547

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.V564F (c.1690G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [10]

• Resistant Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: Ishikawa cells; Endometrium; Homo sapiens (Human); CVCL_2529
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: MOLM-1 cells; Bone marrow; Homo sapiens (Human); CVCL_2188
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vivo Model: Female balb/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Phospho-kinase array analysis; Reporter gene assay; Microarray analysis; RT-PCR; Gene set enrichment analysis
• Experiment for Drug Resistance: MTT assay; Soft-agar colony assay

Disease Class: Endometrial adenocarcinoma [10]

• Resistant Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Resistant Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: Ishikawa cells; Endometrium; Homo sapiens (Human); CVCL_2529
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: MOLM-1 cells; Bone marrow; Homo sapiens (Human); CVCL_2188
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vivo Model: Female balb/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Phospho-kinase array analysis; Reporter gene assay; Microarray analysis; RT-PCR; Gene set enrichment analysis
• Experiment for Drug Resistance: MTT assay; Soft-agar colony assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of AZD-4547 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of AZD-4547 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: AZD-4547
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of AZD-4547 by aberration of the drug's therapeutic target

DEBIO-1347

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.V564I (c.1690G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.V564L (c.1690G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Endometrial adenocarcinoma [9]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Solid tumour/cancer [9]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.V564F (c.1690G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Disease Class: Endometrial adenocarcinoma [9]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: DEBIO-1347
• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

RO-5126766 free base

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [8]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: RO-5126766 free base
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: SUM-52PE cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: NCI-H1581 cells; Lung; Homo sapiens (Human); CVCL_1479
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: KMS-11 cells; Pleural effusion; Homo sapiens (Human); CVCL_2989
• In Vitro Model: HSC-39 cells; Ascites; Homo sapiens (Human); CVCL_A385
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: KATO-III cells; Pleural effusion; Homo sapiens (Human); CVCL_0371
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• Experiment for Molecule Alteration: Microarray assay; Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

PRN1371

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [11]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: PRN1371
• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Disease Class: Solid tumour/cancer [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PRN1371
• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Disease Class: Solid tumour/cancer [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PRN1371
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Disease Class: Solid tumour/cancer [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PRN1371
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Preclinical Drug(s) 3 drug(s) in total

E7090

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Endometrial adenocarcinoma [12]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: E7090
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Identified from the Human Clinical Data

FIIN-1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Endometrial adenocarcinoma [13]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: FIIN-1
• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Drug Resistance: CellTiter-Glo Luminescent Cell Viability Assay
• Mechanism Description: The missense mutation p.N549K (c.1647T>G) in gene FGFR2 cause the sensitivity of FIIN-1 by aberration of the drug's therapeutic target

GSK3052230

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Endometrial adenocarcinoma [14]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: GSK3052230
• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Lung; .
• Experiment for Molecule Alteration: QuantiGene Plex DNA assay
• Mechanism Description: The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of GSK3052230 by aberration of the drug's therapeutic target

Investigative Drug(s) 3 drug(s) in total

Dovitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.M538I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.M536I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.L618M
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.I548V
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.M538I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.M536I
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.L618M
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

Disease Class: Intrahepatic cholangiocarcinoma [15]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: Dovitinib
• Molecule Alteration: Missense mutation; p.I548V
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Within the FGFR2 gene, mutations such as M536I, M538I, I548V and L618M have been shown through in vitro experiments to confer resistance to drugs like dovitinib.

PD173074

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.M536I (c.1608G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.M536I (c.1608G>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.M538I (c.1614G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.M538I (c.1614G>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.I548V (c.1642A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.I548V (c.1642A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.N550H (c.1648A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550H (c.1648A>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.N550S (c.1649A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550S (c.1649A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550K (c.1650T>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.V565I (c.1693G>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.V565I (c.1693G>A) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.E566G (c.1697A>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.E566G (c.1697A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD173074
• Molecule Alteration: Missense mutation; p.L618M (c.1852T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.L618M (c.1852T>A) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Endometrial adenocarcinoma [17]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: PD173074
• Molecule Alteration: Missense mutation; p.N550K (c.1650T>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Uterus; .
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: The missense mutation p.N550K (c.1650T>A) in gene FGFR2 cause the sensitivity of PD173074 by aberration of the drug's therapeutic target

TAS-120

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: TAS-120
• Molecule Alteration: Missense mutation; p.V565F
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Resistant Drug: TAS-120
• Molecule Alteration: Missense mutation; p.V565F
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Sensitive Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Sensitive Drug: TAS-120
• Molecule Alteration: Missense mutation; p.V565I
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Sensitive Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Sensitive Drug: TAS-120
• Molecule Alteration: Missense mutation; p.N550H
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Sensitive Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Sensitive Drug: TAS-120
• Molecule Alteration: Missense mutation; p.E566A
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Sensitive Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Sensitive Drug: TAS-120
• Molecule Alteration: Missense mutation; p.V565I
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Sensitive Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Sensitive Drug: TAS-120
• Molecule Alteration: Missense mutation; p.N550H
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease Class: Intrahepatic cholangiocarcinoma [18]

• Sensitive Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
• Sensitive Drug: TAS-120
• Molecule Alteration: Missense mutation; p.E566A
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ctDNA analysis
• Mechanism Description: TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion-positive intrahepatic cholangiocarcinoma.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.05E-02; Fold-change: -3.93E-01; Z-score: -2.58E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.58E-01; Fold-change: 1.51E-01; Z-score: 4.34E-01

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.43E-08; Fold-change: -5.15E-01; Z-score: -1.54E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.65E-21; Fold-change: -3.90E-01; Z-score: -1.47E+00
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 4.23E-01; Fold-change: -1.46E-01; Z-score: -7.34E-01

References

• Ref 1: Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive CholangiocarcinomaCancer Discov. 2017 Mar;7(3):252-263. doi: 10.1158/2159-8290.CD-16-1000. Epub 2016 Dec 29.
• Ref 2: Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinomaCancer Res. 2013 Aug 15;73(16):5195-205. doi: 10.1158/0008-5472.CAN-12-3950. Epub 2013 Jun 20.
• Ref 3: Identification of Oncogenic and Drug-Sensitizing Mutations in the Extracellular Domain of FGFR2Cancer Res. 2015 Aug 1;75(15):3139-46. doi: 10.1158/0008-5472.CAN-14-3771. Epub 2015 Jun 5.
• Ref 4: miR 494 inhibits cancer initiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2 positive gastric cancer. Int J Mol Med. 2018 Aug;42(2):998-1007. doi: 10.3892/ijmm.2018.3680. Epub 2018 May 16.
• Ref 5: Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib .Cancer Discov. 2021 Feb;11(2):326-339. doi: 10.1158/2159-8290.CD-20-0766. Epub 2020 Nov 20. 10.1158/2159-8290.CD-20-0766
• Ref 6: Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer modelsMol Cancer Ther. 2012 Mar;11(3):690-9. doi: 10.1158/1535-7163.MCT-11-0450. Epub 2012 Jan 11.
• Ref 7: Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR DysregulationPLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. eCollection 2016.
• Ref 8: ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR InhibitorMol Cancer Ther. 2015 Dec;14(12):2831-9. doi: 10.1158/1535-7163.MCT-15-0497. Epub 2015 Oct 5.
• Ref 9: The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitorMol Cancer Ther. 2014 Nov;13(11):2547-58. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28.
• Ref 10: Antitumor Effects and Mechanisms of AZD4547 on FGFR2-Deregulated Endometrial Cancer CellsMol Cancer Ther. 2015 Oct;14(10):2292-302. doi: 10.1158/1535-7163.MCT-15-0032. Epub 2015 Aug 20.
• Ref 11: The Irreversible Covalent Fibroblast Growth Factor Receptor Inhibitor PRN1371 Exhibits Sustained Inhibition of FGFR after Drug ClearanceMol Cancer Ther. 2017 Dec;16(12):2668-2676. doi: 10.1158/1535-7163.MCT-17-0309. Epub 2017 Oct 4.
• Ref 12: E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical ModelsMol Cancer Ther. 2016 Nov;15(11):2630-2639. doi: 10.1158/1535-7163.MCT-16-0261. Epub 2016 Aug 17.
• Ref 13: A structure-guided approach to creating covalent FGFR inhibitorsChem Biol. 2010 Mar 26;17(3):285-95. doi: 10.1016/j.chembiol.2010.02.007.
• Ref 14: Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancerSci Transl Med. 2013 Mar 27;5(178):178ra39. doi: 10.1126/scitranslmed.3005414.
• Ref 15: Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance .Br J Cancer. 2021 Mar;124(5):880-892. doi: 10.1038/s41416-020-01157-0. Epub 2020 Dec 3. 10.1038/s41416-020-01157-0
• Ref 16: The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitorsNeoplasia. 2013 Aug;15(8):975-88. doi: 10.1593/neo.121106.
• Ref 17: Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogationCancer Res. 2008 Sep 1;68(17):6902-7. doi: 10.1158/0008-5472.CAN-08-0770.
• Ref 18: TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma .Cancer Discov. 2019 Aug;9(8):1064-1079. doi: 10.1158/2159-8290.CD-19-0182. Epub 2019 May 20. 10.1158/2159-8290.CD-19-0182