Achievements and challenges of molecular targeted therapy in melanoma
June 26, 2015
Key Points
- The great majority of patients with melanoma have mutations in genes (oncogenes and/or tumor suppressor genes) that drive MAPK pathway activation.
- Potent and specific inhibitors of MAPK pathway mediators have been discovered and include BRAF inhibitors (vemurafenib, dabrafenib, encorafenib), MEK inhibitors (trametinib, selumetinib, cobimetinib, binimetinib), ERK inhibitors (BVD-523, GDC-0994), and pan-RAF inhibitors (LY3009120).
- Combination BRAF/MEK inhibition is superior to single-agent BRAF inhibition in patients withBRAFV600-mutant melanoma; a number of trials of BRAF/MEK inhibition plus a third targeted agent are underway to determine whether triplet therapy is superior to BRAF/MEK doublet therapy.
- Single-agent pan-RAF, MEK, and ERK inhibitor therapies may be effective strategies for the treatment of other molecular subsets of melanoma, including uveal melanoma (typically eitherGNAQorGNA11mutant),NRAS-mutant,MEK-mutant, non-V600BRAFmutant, andNF-1loss of function.
- The use of novel molecular targeted therapies, alone or in combination, holds great promise for the treatment of melanoma, but is not without challenges.
Source:
Sullivan,
R, et al. Achievements and challenges of molecular targeted therapy in
melanoma.
http://meetinglibrary.asco.org/content/115000177-156
- Neoadjuvant Therapy for Melanoma: A Promising Therapeutic Approach and an Ideal Platform in Drug Development http://meetinglibrary.asco.org/content/11500535-156
- Merkel Cell Carcinoma: Emerging Biology, Current Approaches, and Future Directions
http://meetinglibrary.asco.org/content/11500519-15... - Perfusion and Infusion for Melanoma In-Transit Metastases in the Era of Effective Systemic Therapy
http://meetinglibrary.asco.org/content/11500528-156
- Prognostic Factors and the Role of Adjuvant
Radiation Therapy in Non-Melanoma Skin Cancer of
the Head and Neck