Table 1.
FDA-approved targeted cancer drugs in clinical use that are dependent for activity on the presence of a genomic alteration in the patient's tumour. Approved small molecule inhibitors and antibodies targeting specific drug-sensitizing mutations in human cancers. Although these mutations dramatically affect the likelihood of a given patient responding to a particular therapy, it is pertinent to note that in many cases these mutations are only present in a subset of that specific tumour type. Identification of these subgroups using next-generation sequencing technologies will become increasingly important for the management of cancer patients in the clinic
Tumour | Gene (mutation) | Prevalence of gene alteration (%) | FDA-approved drug | Year approved | Therapeutic target | Response rate in mutant tumours (%) | Study |
---|---|---|---|---|---|---|---|
Chronic myeloid leukaemia | BCR-ABL (translocation) | >95 | Imatinib | 2001 | ABL1 | >95 | Druker et al. [4] |
Gastrointestinal stromal tumour | KIT (mutation), PDGFRA (mutation) | 85 (KIT), 5–8 (PDGFRA) | Imatinib | 2002 | KIT, PDGFRA | >80 | Verweij et al. [8] |
Non-small cell lung cancer | EGFR (mutation) | 10 | Gefitinib, erlotinib | 2003, 2004 | EGFR | 70 | Mok et al. [6] |
Chronic myeloid leukaemia (imatinib-resistant) | BCR-ABL (translocation) | >95 | Dasatanib | 2006 | ABL1 | >90 | Talpaz et al. [7] |
Breast cancer–node +ve | HER2 amplification | 15–20 | Trastuzunab | 2006 | ERBB2 | HR 0.48 | Perez et al. [13] |
Melanoma | BRAF (mutation) | 40–70 | Vemurafenib | 2011 | BRAF | >50 | Chapman et al. [20] |
Non-small cell lung cancer | EML4-ALK (translocation) | 2-7 | Crizotinib | 2011 | ALK | 57 | Kwak et al. [5] |
Melanoma | BRAF (mutation) | 40–70 | Debrafenib | 2013 | BRAF | 52 | Hauschild et al. [10] |
Melanoma | BRAF (mutation) | 40–70 | Trametinib | 2013 | MEK1 | 22 | Flaherty et al. [11] |
Non-small cell lung cancer | EGFR (mutation) | 10 | Afatinib | 2013 | EGFR/ERBB2 | 50 | Yang et al. [12] |
Breast cancer (metastatic) | HER2 amplification | 15–20 | Trastuzumab | 2013 | ERBB2 | 44 | Verma et al. [14] |
Abbreviations: KIT, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homologue; PDGFRA, platelet-derived growth factor receptor; alpha polypeptide.