Drug Information

Drug (ID: DG01864) and It's Reported Resistant Information

• Name: PI3K pathway inhibitors
• Synonyms: PI3K pathway inhibitors
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
• Target: .; NOUNIPROTAC; [3]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Copy number gain; .
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter Glo luminescence assay; PathScan RTK signaling antibody array assay

Key Molecule: PI3-kinase beta (PIK3CB) [2]

• Molecule Alteration: Missense mutation; p.D1067Y (c.3199G>T)
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: SUM-52PE cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: Rat2 cells; Whole embryo; Rattus norvegicus (Rat); CVCL_0513
• In Vitro Model: HCC-1569 cells; Breast; Homo sapiens (Human); CVCL_1255
• In Vitro Model: EVSA-T cells; Ascites; Homo sapiens (Human); CVCL_1207
• In Vitro Model: A-498 cells; Kidney; Homo sapiens (Human); CVCL_1056
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: phosphoinositide-3-dependent protein kinase 1 (PDPK1) [4]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Breast; N.A.
• In Vivo Model: SCID/NCr (BALB/c background) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The copy number gain in gene PDPK1 cause the sensitivity of PI3K pathway inhibitors by unusual activation of pro-survival pathway.

Head and neck cancer [ICD-11: 2D42]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [3]

• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• 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

References

• Ref 1: Acquired PIK3CA amplification causes resistance to selective phosphoinositide 3-kinase inhibitors in breast cancerOncogenesis. 2013 Dec 23;2(12):e83. doi: 10.1038/oncsis.2013.46.
• Ref 2: Activating Mutations in PIK3CB Confer Resistance to PI3K Inhibition and Define a Novel Oncogenic Role for p110BetaCancer Res. 2016 Mar 1;76(5):1193-203. doi: 10.1158/0008-5472.CAN-15-2201. Epub 2016 Jan 12.
• Ref 3: Incorporation of Next-Generation Sequencing into Routine Clinical Care to Direct Treatment of Head and Neck Squamous Cell CarcinomaClin Cancer Res. 2016 Jun 15;22(12):2939-49. doi: 10.1158/1078-0432.CCR-15-2314. Epub 2016 Jan 13.
• Ref 4: 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinomaCancer Res. 2009 Aug 1;69(15):6299-306. doi: 10.1158/0008-5472.CAN-09-0820. Epub 2009 Jul 14.