Disease Information

General Information of the Disease (ID: DIS00103)

• Name: Head and neck cancer
• ICD: ICD-11: 2D42

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 11 drug(s) in total

Cetuximab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-212 [1]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cetuximab
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SCC1 cells; Tongue; Homo sapiens (Human); CVCL_A5SA
• In Vitro Model: 1Cc8 cells; Epithelium; Homo sapiens (Human); CVCL_L893
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: HB-EGF can induce EMT, enhance metastasis, and modulate chemotherapy resistance. Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Proheparin-binding EGF-like growth factor (HBEGF) [1]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cetuximab
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SCC1 cells; Tongue; Homo sapiens (Human); CVCL_A5SA
• In Vitro Model: 1Cc8 cells; Epithelium; Homo sapiens (Human); CVCL_L893
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: HB-EGF can induce EMT, enhance metastasis, and modulate chemotherapy resistance. Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-204 [2]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cetuximab
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAKT2/STAT3 signaling pathway; Inhibition; hsa04030
• In Vitro Model: 5-8F cells; Nasopharynx; Homo sapiens (Human); CVCL_C528
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAk2-STAT3 signaling.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cetuximab
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAKT2/STAT3 signaling pathway; Inhibition; hsa04030
• In Vitro Model: 5-8F cells; Nasopharynx; Homo sapiens (Human); CVCL_C528
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAk2-STAT3 signaling.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Cyclin-dependent kinase inhibitor 1B (CDKN1B) [3]

• Resistant Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Exosomal miR-196a promotes cisplatin resistance in HNC cells through CDkN1B and ING5 downregulation.

Key Molecule: Growth protein 5 inhibitor (ING5) [3]

• Resistant Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Exosomal miR-196a promotes cisplatin resistance in HNC cells through CDkN1B and ING5 downregulation.

Key Molecule: hsa-mir-196a [3]

• Resistant Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Exosomal miR-196a promotes cisplatin resistance in HNC cells through CDkN1B and ING5 downregulation.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-let-7d [4]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Clonogenic assay; MTT assay
• Mechanism Description: The level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics. Overexpressed let-7d inhibited chemoresistance to cisplatin and paclitaxel in OSCC-ALDH1+ cells.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [5]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Inhibition; hsa04150
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell survival; Activation; hsa05200
• Cell Pathway Regulation: IL-1beta/IL-8/CXCR1 signaling pathway; Inhibition; hsa04060
• In Vitro Model: GNM cells; Oral; Homo sapiens (Human); CVCL_WL58
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• In Vivo Model: BALB/c nude mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Oral cancer cells with sh-LINC00963 exhibited lower resistance to cisplatin or 5-FU compared to sh-Luc control. Moreover, the percentage and protein expression level of ABCB5 (ATP-binding cassette, subfamily B (MDR/TAP), member 5) was significantly reduced in both SAS and GNM cells with sh-LINC00963 knockdown. As an ATP-binding cassette transporter, ABCB5 has been known to act as a drug efflux transporter and confer multidrug resistance in diverse malign.

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-let-7d [4]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Clonogenic assay; MTT assay
• Mechanism Description: The level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics. Overexpressed let-7d inhibited chemoresistance to cisplatin and paclitaxel in OSCC-ALDH1+ cells.

Erlotinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-34 [6]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Erlotinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: HN5 cells; Neck; Homo sapiens (Human); CVCL_8128
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Expression of the tumor suppressor miR-34a was reduced in HN5-ER cells and increasing its expression abrogated Axl expression and reversed erlotinib resistance.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin 2 receptor subunit alpha (IL2RA) [7]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Etoposide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PCI-13 cells; Ovary; Homo sapiens (Human); CVCL_C182
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: IL-2Ralpha-expressing cells were significantly more resistant to apoptosis induction by a tripeptidyl proteasome inhibitor (ALLN) and two chemotherapeutic drugs (VP-16 and taxol) than the control or IL-2Rgamma+ cells.IL-2Ralpha overexpression increases cell proliferation rate associated with increasing levels of cell cycle regulatory proteins.

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-let-7d [4]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Clonogenic assay; MTT assay
• Mechanism Description: The level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics. Overexpressed let-7d inhibited chemoresistance to cisplatin and paclitaxel in OSCC-ALDH1+ cells.

Key Molecule: hsa-miR-24-3p [8]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: miR-24-3p is involved in regulating cell proliferation, clonogenecity and chemosensitivity in HNSCC cells. CHD5 is the critical downstream mediator implicated in this regulation. Importantly, miR-24-3p is upregulated in HNSCC patient samples. Inhibition of miR-24-3p conferred sensitivity to chemo drugs which was reversed with CHD5 knockdown.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Chromodomain-helicase-DNA-binding protein 5 (CHD5) [8]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Fluorouracil
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• Experiment for Molecule Alteration: Northern blotting
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: miR-24-3p is involved in regulating cell proliferation, clonogenecity and chemosensitivity in HNSCC cells. CHD5 is the critical downstream mediator implicated in this regulation. Importantly, miR-24-3p is upregulated in HNSCC patient samples. Inhibition of miR-24-3p conferred sensitivity to chemo drugs which was reversed with CHD5 knockdown.

Infigratinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [9]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.S131L (c.392C>T)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: HN cells; Cervical lymph node; Homo sapiens (Human); CVCL_1283
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: 584-A2 cells; Larynx; Homo sapiens (Human); CVCL_V278
• Experiment for Molecule Alteration: Immunohistochemical staining assay; qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: In vitro, FGFR3 overexpression led to increased proliferation, whereas migration was not altered. Moreover, FGFR3-overexpressing cells were more sensitive to BGJ398. Cells overexpressing FGFR3 mutant versions showed increased proliferation compared to wild-type FGFR3 under serum-reduced conditions and were largely as sensitive as the wild-type protein to BGJ398.

Interferon alfa-2B

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: MX dynamin like GTPase 1 (MX1) [10]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Interferon alfa-2B
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HN30 cells; Nasopharyngeal; Homo sapiens (Human); CVCL_5525
• In Vitro Model: HN4 cells; Nasopharyngeal; Homo sapiens (Human); CVCL_IS30
• In Vitro Model: HN6 cells; Tongue; Homo sapiens (Human); CVCL_8129
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Overexpression assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: LncMX1-215 negatively regulates immunosuppression by interrupting GCN5/H3K27ac binding in HNSCC.

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin 2 receptor subunit alpha (IL2RA) [7]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Paclitaxel
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PCI-13 cells; Ovary; Homo sapiens (Human); CVCL_C182
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: IL-2Ralpha-expressing cells were significantly more resistant to apoptosis induction by a tripeptidyl proteasome inhibitor (ALLN) and two chemotherapeutic drugs (VP-16 and taxol) than the control or IL-2Rgamma+ cells.IL-2Ralpha overexpression increases cell proliferation rate associated with increasing levels of cell cycle regulatory proteins.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-let-7d [4]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Clonogenic assay; MTT assay
• Mechanism Description: The level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics. Overexpressed let-7d inhibited chemoresistance to cisplatin and paclitaxel in OSCC-ALDH1+ cells.

Trametinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Transcriptional coactivator YAP1 (YAP1) [11]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: SH-1-V5 cells; Esophagus; Homo sapiens (Human); N.A.
• In Vivo Model: Patient-derived xenografts in female NSG mouse model; Mus musculus
• Mechanism Description: Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas. This study identify a Yap1-dependent resistance to trametinib therapy in HNSCCs. Combined Yap1 and MEK targeting may represent a strategy to enhance HNSCC response.

Trastuzumab-based chemotherapy

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [12]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Copy number gain; .
• Sensitive Drug: Trastuzumab-based chemotherapy
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human salivary ductal carcinoma tissue; .
• Mechanism Description: The copy number gain in gene ERBB2 cause the sensitivity of Trastuzumab-based chemotherapy by aberration of the drug's therapeutic target.

Clinical Trial Drug(s) 5 drug(s) in total

Rigosertib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [13]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Drug: Rigosertib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HNSCC cells; Neck; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Sulforhodamine B colorimetric assay
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of Rigosertib by aberration of the drug's therapeutic target

Taselisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [14]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: Taselisib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• In Vitro Model: UPCI-SCC-90 cells; Tongue; Homo sapiens (Human); CVCL_1899
• In Vitro Model: UPCI-SCC-154 cells; Tongue; Homo sapiens (Human); CVCL_2230
• In Vitro Model: UM-SCC-47 cells; Tongue; Homo sapiens (Human); CVCL_7759
• In Vitro Model: UM-SCC-104 cells; Cervical lymph node; Homo sapiens (Human); CVCL_7712
• In Vitro Model: UD-SCC-2 cells; Neck; Homo sapiens (Human); CVCL_E325
• In Vitro Model: SNU46 cells; Larynx; Homo sapiens (Human); CVCL_5063
• In Vitro Model: SNU cells; Stomach; Homo sapiens (Human); CVCL_0099
• In Vitro Model: HSC-4 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1289
• In Vitro Model: HSC-3 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HSC-2 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1287
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: Cal-33 cells; Tongue; Homo sapiens (Human); CVCL_1108
• In Vitro Model: BICR-31 cells; Tongue; Homo sapiens (Human); CVCL_2312
• In Vitro Model: BICR-22 cells; Lymph node; Homo sapiens (Human); CVCL_2310
• In Vitro Model: BICR-18 cells; Lymph Node; Homo sapiens (Human); CVCL_2309
• In Vitro Model: BICR-16 cells; Tongue; Homo sapiens (Human); CVCL_2308
• In Vitro Model: 93-VU-147T cells; Oral cavity; Homo sapiens (Human); CVCL_L895
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Crystal violet staining assay

Apitolisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [15]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.E542K (c.1624G>A)
• Sensitive Drug: Apitolisib
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DxS allele-specific PCR; qRT-PCR assays; Sanger sequencing assay
• Experiment for Drug Resistance: CTCAE assay

Ulixertinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [16]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Missense mutation; p.G469A (c.1406G>C)
• Sensitive Drug: Ulixertinib
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010

WNT-974

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [17]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.C478F (c.1433G>T)
• Sensitive Drug: WNT-974
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: HN30 cells; Nasopharyngeal; Homo sapiens (Human); CVCL_5525
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC25 cells; Oral; Homo sapiens (Human); CVCL_1682
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vitro Model: UMSCC cells; Oral cavity; Homo sapiens (Human); CVCL_7707
• In Vitro Model: Hs840T cells; Pharynx; Homo sapiens (Human); CVCL_0942
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: A-253 cells; Salivary gland; Homo sapiens (Human); CVCL_1060
• In Vitro Model: SCC-4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• In Vitro Model: Hs840.T cells; N.A.; .; N.A.
• In Vivo Model: Nude mouse(or nude rat) xenograft model; Mus musculus
• Experiment for Molecule Alteration: TaqMan assay
• Experiment for Drug Resistance: Colony formation assay

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

ReACp53

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [18]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Sensitive Drug: ReACp53
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: S1 GODL cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Immunocompromised NSG mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: In vitro 3D organoid assay

SHR-A1307

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase alpha (PIK3CA) [19]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: SHR-A1307
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: DiFi cells; Colon; Homo sapiens (Human); CVCL_6895
• In Vitro Model: Detroit562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vitro Model: Colo-205 cells; Ascites; Homo sapiens (Human); CVCL_0218
• In Vivo Model: Female BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Sirolimus/Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [20]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Sensitive Drug: Sirolimus/Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: UM-SCC-17B cells; Cervical lymph node; Homo sapiens (Human); CVCL_7725
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vivo Model: Athymic nude mouse tumor xenografts model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue cell viability reagent assay
• Mechanism Description: mTOR and MEK inhibition display a synergistic growth inhibitory activity in HNSCC cells genetically engineered to express activating KRAS and PIK3CA mutations. Antitumoral activity of the rapamycin and trametinib combination therapy increase in genetically engineered HNSCC cells expressing activating RAS or PIK3CA mutations

Key Molecule: PI3-kinase alpha (PIK3CA) [20]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: Sirolimus/Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/mTOR signaling pathway; Inhibition; hsa04151
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: UM-SCC-17B cells; Cervical lymph node; Homo sapiens (Human); CVCL_7725
• In Vitro Model: Detroit 562 cells; Pleural effusion; Homo sapiens (Human); CVCL_1171
• In Vivo Model: Athymic nude mouse tumor xenografts model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue cell viability reagent assay
• Mechanism Description: mTOR and MEK inhibition display a synergistic growth inhibitory activity in HNSCC cells genetically engineered to express activating KRAS and PIK3CA mutations. Antitumoral activity of the rapamycin and trametinib combination therapy increase in genetically engineered HNSCC cells expressing activating RAS or PIK3CA mutations

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

D-Allosamine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin 2 receptor subunit alpha (IL2RA) [7]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: D-Allosamine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PCI-13 cells; Ovary; Homo sapiens (Human); CVCL_C182
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: IL-2Ralpha-expressing cells were significantly more resistant to apoptosis induction by a tripeptidyl proteasome inhibitor (ALLN) and two chemotherapeutic drugs (VP-16 and taxol) than the control or IL-2Rgamma+ cells.IL-2Ralpha overexpression increases cell proliferation rate associated with increasing levels of cell cycle regulatory proteins.

ERK inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [21]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Missense mutation; p.G469A (c.1454T>G)
• Sensitive Drug: ERK inhibitors
• Experimental Note: Identified from the Human Clinical Data

PI3K pathway inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [22]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Drug: PI3K pathway inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of PI3K pathway inhibitors by aberration of the drug's therapeutic target

PKI-587

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [23]

• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: PKI-587
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: UMSCC cells; Oral cavity; Homo sapiens (Human); CVCL_7707
• In Vivo Model: SCID/NCr-Balb/c mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; qPCR
• Experiment for Drug Resistance: XTT assay

References

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