BRAF and MEK inhibitors in therapy of advanced melanoma

Abstract

Metastatic melanoma is a highly lethal malignancy. Standard treatment modalities didn’t have any impact on overall survival. Recent studies and improvement in recognition of mechanisms responsible for tumor progression resulted in introduction of new therapeutic modalities such as immunotherapy or drugs molecularly targeted. Support for the molecular studies was the discovery that more than a half of melanoma patients carry a mutation in gene encoding BRAF, which is a component of MAPK pathway responsible for cancer development. This mutation is associated with a specific clinic-pathological features and a more aggressive behavior in stage 4 disease. First attempts to block BRAF, with the use of multi-kinase inhibitor sorafenib, was a failure. Studies on more specific BRAF inhibitors showed high effectiveness with acceptable side effects in patients with confirmed BRAF mutation. They were the basis for registration of one of the drugs in USA. Challenging in BRAF therapy is quite rapidly occurring resistance to treatment, that is responsible for the short time to progression in patients that initially have benefit from the treatment. One of the solutions to the problem can be using MEK inhibitors, that block another step in the MAPK pathway. They didn’t show high efficiency in melanoma therapy, but possibly they will be very helpful in overcoming resistance to BRAF inhibitors.
Onkol. Prak. Klin. 2011; 7, 5: 246–253