Cancer Science & Therapy

Melanoma Metamorphoses: Advances in Biology and Therapy

Abstract

Arthur E. Frankel and Eugene P. Frenkel

Melanoma is a malignancy of melanocytes of cutaneous, uveal or mucosal origins. This review discusses advances in biology and new approaches in staging and advanced disease therapy. The role of UVA light in dark reactions generating dioxetane products and cyclobutane pyrimidine dimers in melanoma genesis is detailed. Utility of screening programs and prevention with enhanced UVA blockers is included. Different staging algorithms for cutaneous, uveal and mucosal melanomas are described. Advances in adjuvant radiotherapy and immunotherapy are noted. Stereotactic radiotherapy for brain metastases and metastasectomy for oligometastatic disease has impacted the natural history of this disease. While combined BRAF and MEK inhibition for BRAF mutant melanoma patients have produced durable remissions, relapse is frequent and due to multiple genetic mechanisms. Immunotherapy with anti-CTLA4 and anti-PD1 immune checkpoint blockers also yields long-term responses, but there remains many patients unresponsive to immune checkpoint blockade or whom develop resistance. Host and tumor-specific resistance mechanisms are explored. Some new areas of melanoma research include nanoparticle fluorescence surgical imaging for regional and metastatic disease, tumor gene expression profiling to predict BRAF inhibitor resistance, combination of ion channel blocker with MEK inhibitor for wild-type BRAF metastatic melanoma, establishment of the innate immune signalling pathway for stereotactic radiotherapy of melanoma, and testing of IDO inhibitors with anti-PD1 inhibitors in metastatic melanoma.