TABLE 1

Activating genetic alterations of tyrosine kinases and FDA-approved targeted inhibitors in human malignanciesa

Genetic alterationKinaseDisease(s)FDA-approved inhibitor(s)
Mutation(s)
    Exons 19, 21EGFRNSCLCErlotinib, afatinib
    Exons 8, 9, 11, 13, 17c-KITGISTImatinib, sunitinib
    Exons 12, 14, 18PDGFRαGISTImatinib, sunitinib
    Exons 10, 11, 13, 14RETMedullary thyroid carcinomaVandetinib, cabozantinib
    V617FJAK2Myeloproliferative neoplasmsRuxolitinib
Translocation(s)
    BCR-ABL1 fusionABL1CMLImatinib, dasatinib, nilotinib, bosutinib, ponatinib
    RET/PTC family fusionsRETPTCVandetinib
    EML4-ALK fusionALKNSCLCCrizotinib
Amplification(s): increased copy no. and/or overexpressionERBB2Breast cancer, gastric cancerTrastuzumab, lapatinib, ado-trastuzumab emtansine, pertuzumab
Pathway activation
    B-cell receptor signalingBTKCLLIbrutinib
B-cell non-Hodgkin's lymphoma
    AngiogenesisVEGFRCCRCC, soft-tissue carcinomaSorafenib, sunitinib, pazopanib, axitinib
  • a Abbreviations: NSCLC, non-small-cell lung cancer; GIST, gastrointestinal stromal tumor; CML, chronic myelogenous leukemia; PTC, papillary thyroid carcinoma; CCRCC, clear cell renal cell carcinoma; CLL, chronic lymphocytic leukemia.