WASHINGTON, D.C. — Scientists have identified biomarkers that may help predict whether patients with KRAS-mutated non-small cell lung cancer (NSCLC) will respond to concurrent treatment with an MEK inhibitor and a PI3 kinase inhibitor, a drug…
“The mechanisms underlying adaptive resistance of melanoma to targeted therapies remain unclear. By combining ChIP sequencing with microarray-based gene profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription factor that promotes resistance to RAF inhibitors in melanoma…”
Using a panel of non-small cell lung cancer (NSCLC) lines, we show here that MEK and RAF inhibitors are selectively toxic for the KRAS mutant genotype, while PI 3-kinase (PI3K), AKT and mTOR inhibitors are not. Coordinate direct input of both KRAS and IGF1R is required to activate PI3K in KRAS mutant lung cancer cells.
A clinical trial found that dabrafenib, a BRAF inhibitor, was far more effective in treating melanomas that have BRAF mutations than the chemotherapy drug dacarbazine, according to a report at an American Society of Clinical Oncology meeting. Patients treated with this drug lived without getting worse for 70% longer than those treated with dacarbazine (5.1 vs. 2.7 months, respectively). Moreover, compared to those treated with vemurafenib in other studies, dabrafenib-treated patients had less risk of another kind of skin cancer called squamous cell carcinoma. This suggests that dabrafenib, which is experimental, could be safer than vemurafenib, which is FDA approved.
A New England Journal of Medicine study found that vemurafenib, which was approved by the FDA in 2011, controlled melanomas in about half of people who had been previously treated for this disease. The trial included 132 repeat patients; tumors shrank in 47% of the patients and were not evident in 6% during the course of the trial. Vemurafenib is a BRAF inhibitor and about half of melanoma patients have BRAF mutations. While 26% of patients developed another kind of skin cancer called squamous cell carcinoma, these lesions were successfully removed surgically.
Primary source: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1112302