Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials


Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

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Jeter JM, Bowles TL, Curiel-Lewandrowski C, Swetter SM, Filipp FV, Abdel-Malek ZA, Geskin LJ, Brewer JD, Arbiser JL, Gershenwald JE, Chu EY, Kirkwood JM, Box NF, Funchain P, Fisher DE, Kendra KL, Marghoob AA, Chen SC, Ming ME, Albertini MR, Vetto JT, Margolin KA, Pagoto SL, Hay JL, Grossman D, Ellis DL, Kashani-Sabet M, Mangold AR, Markovic SN, Nelson KC, Powers JG, Robinson JK, Sahni D, Sekulic A, Sondak VK, Wei ML, Zager JS, Dellavalle RP, Thompson JA, Weinstock MA, Leachman SA, Cassidy PB. Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials. Cancer. 2019 Jan 1;125(1):18-44. doi: 10.1002/cncr.31719. Epub 2018 Oct 3. Review. Erratum in: Cancer. 2019 Aug 1;125(15):2706. PubMed PMID: 30281145.

Keywords: biomarkers; chemoprevention; human model systems; melanoma; natural products; clinical trials; developing (or repurposing) drugs and natural products; keratinocyte carcinoma chemoprevention studies.

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