Initial systemic therapies for cancer focused on the use of cytotoxic agents. The aim was to preferentially eradicate faster-dividing cancer cells while sparing normal cells. Although such treatments have successfully treated some cancers, melanomas are among the cancers least likely to be cured by chemotherapy.
Over recent decades, research has elucidated the molecular processes involved in cancer, including cell survival, migration, proliferation, and apoptosis. Drugs directed at modulating these processes in the cancer cells as well as drugs targeting the host’s response to the cancer (e.g., anti-angiogenesis and immune therapies) achieved varying degrees of success, resulting in the approval of many new cancer drugs, but again, precious few for melanoma.
That all changed over the past year with the approval of YervoyTM and ZelborafTM. In this issue of The Melanoma Letter, Dr. Paul Chapman discusses the exciting, newly FDA-approved drug ZelborafTM (vemurafenib), which targets a unique mutation in the BRAF gene that is remarkably common among patients with advanced melanoma. The striking responses of many patients to this drug serve as a beacon of hope that someday treatments will become available that will truly eliminate advanced melanomas and lead to genuine ‘cures’.
Research is already under way to determine whether combining BRAF inhibitors with other therapies such as ipilimumab (YervoyTM) may offer therapeutic benefit to more patients afflicted with melanoma. It is becoming abundantly clear that selecting optimum therapy will involve determining the “driver” mutation in a given patient’s melanoma, such as BRAF or cKit, and targeting it with a specific drug. The more we learn about the molecular underpinnings of melanoma and the mechanisms by which the new therapies that target them succeed and fail, the greater the optimism grows for clinicians, researchers, and the patients they seek to save.
Allan C. Halpern, MD
Ashfaq A. Marghoob, MD