Tumors harboring these mutations may respond to a selective BRAF inhibitor[6], [9].
Infants with KCNJ11 or ABCC8 genetic mutations may respond to oral sulfonylurea therapy.
Patients with KRAS G12V mutations may respond better in terms of change in tumour size at week 6; however, as patient numbers are small, larger clinical studies would be required to test robustly the hypothesis that specific codon status can condition response to therapy.
The clinical observation, that some patients with KRAS mutation may respond to anti-EGFR-antibody therapy, as well as experimental data, that the biological effects of KRAS mutations may differ, was addressed recently by de Roock and Tejpar [ 12, 13].
Since uncommon tumors may be uncommon as a consequence of having only a small number of potential driving mutations [ 12], and since a high proportion of patients with a relevant mutation may respond to a targeted agent (as noted above), then relatively small phase II trials may be reasonable with uncommon malignancies.
Many of these "KIT-negative" GIST harbor PDGFRA mutations and may respond to imatinib treatment [5], [6], hence need to be classified correctly.
There are emerging data which suggest that mutation carriers may respond differently than non-carriers to particular agents [ 1- 3].
Although patients with a BRCA mutation signature may respond to either platinum drugs or PARP inhibitors, there are no curative therapies in PDAC, underscoring the urgent need for innovative therapeutic strategies.
Another mechanism, whereby, tumours with drug-sensitive EGFR mutations may not respond to treatment with EGFR inhibitors is the presence of other genetic lesions that affect signalling downstream of EGFR, including activating mutations in the PIK3CA gene or loss of PTEN expression (Pao and Chmielecki, 2010).
Thus, up to 7%% of lung adenocarcinomas that have acquired somatic mutations that inactivate ATM may respond to single agent therapy with an ATR kinase inhibitor.
PARP inhibitors also show promise in triple-negative breast cancer, as studies have shown that a proportion of these women possess BRCA mutations 68, 69 and may respond to PARP inhibitors.
