FREE ACCESS TO THE LATEST RESEARCH
Welcome to the European Journal of Cancer’s Advances in Melanoma Resource Centre.
The Resource Centre, edited by Prof. Reinhard Dummer, Dr. Paolo Ascierto and Dr. James Larkin, will provide you with the latest research on melanoma, including a selection of original research and review articles from some of the world’s leading journals, case studies, and other educational material.
New articles will be added to the Resource Centre regularly and are openly available to our readers.
Paper of the month – November 2014
Editorial comment by Prof. R. Dummer:
This month we have decided to present two papers. Both papers were published in the New England Journal of Medicine and report on two prospective randomized trials investigating the clinical outcome of a monotherapy with a BRAF inhibitor versus a combination therapy using a BRAF inhibitor and a MEK inhibitor in patients with BRAF mutated advanced melanoma. In both studies there is a clear advantage for the combination therapy with an increase in progression free survival resulting in an improvement of approximately 40% with an improved response rate. The phase III clinical trial presented by Long reached its primary endpoint progression free survival and the secondary endpoint overall survival. Taking together these studies clearly support combination therapy with a BRAF and MEK inhibitor as the standard of care for BRAF mutated melanoma.
Georgina V. Long, M.D., Ph.D., Daniil Stroyakovskiy, M.D., Helen Gogas, M.D., Evgeny Levchenko, M.D., Filippo de Braud, M.D., James Larkin, M.D., Claus Garbe, M.D., Ph.D., Thomas Jouary, M.D., Axel Hauschild, M.D., Ph.D., Jean Jacques Grob, M.D., Ph.D., VN Engl J Med 2014; 371:1877-1888November 13, 2014DOI: 10.1056/NEJMoa1406037
James Larkin, M.D., Ph.D., Paolo A. Ascierto, M.D., Brigitte Dréno, M.D., Ph.D., Victoria Atkinson, M.D., Gabriella Liszkay, M.D., Michele Maio, M.D., Mario Mandalà, M.D., Lev Demidov, M.D., Daniil Stroyakovskiy, M.D., Luc Thomas, M.D., Ph.D., Luis de laN Engl J Med 2014; 371:1867-1876November 13, 2014DOI: 10.1056/NEJMoa1408868
Alexander M Menzies, Georgina V LongReview Article The Lancet Oncology, Volume 15, Issue 9, August 2014, Pages e371-e381
Caputo E, Miceli R, Motti M, Taté R, Fratangelo F, Botti G, Mozzillo N, Carriero M, Cavalcanti E, Palmieri G, Ciliberto G, Pirozzi G, Ascierto P.J Transl Med. 2014 Jul 31;12(1):216. [Epub ahead of print]
In this work it was explored the effect of a triple combination with BRAF and MEK inhibitors together with an Aurora kinase A inhibitor, on a melanoma cell line in a 3D human skin model. For the first time it was observed that BRAF, MEK and AurkA inhibitor triple drug combination may increased efficacy against melanoma cell growth and could be potentially explored in a clinical trial for enhancing clinical response in melanoma
Sara Tomei, Davide Bedognetti, Valeria De Giorgi, Michele Sommariva, Sara Civini, Jennifer Reinboth, Muna Al Hashmi, Maria Libera Ascierto, Qiuzhen Liu, Ben D. Ayotte, Andrea Worschech, Lorenzo Uccellini, Paolo A. Ascierto, David Stroncek, Giuseppe PalmieOriginal Research Article Molecular Oncology, In Press, Uncorrected Proof, Available online 6 August 2014
The role of oncogenes BRAF and NRAS has been extensively described with regard to their ability to promote tumor growth. It is not yet clear their role to influence the modulation of the immune response against the tumor. In this study it was investigated the correlation between the presence NRAS or BRAF mutation, the gene expression profile and the presence of one of the two different immune phenotypes, the Th17 and the Th1, which were previously connected to different classes of prognosis. According to this study, the BRAF mutation was associated with a worse prognosis immunophenotype, while there was no clear correlation between the mutation of NRAS and the context of tumor immunology. Despite the great interest of these results, it remains unclear what are the mechanisms that underlie this association and what are the possible clinical implications.
About the editors
- Professor Dummer is Vice-Chairman of the Department of Dermatology and Head of the Skin Cancer Unit at the University Hospital...
- Dr James Larkin, FRCP PhD is a Medical Oncologist specialising in the treatment of patients with cancer of the kidney...
- Dr. Paolo A. Ascierto is Director at the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, National Tumor Institute ‘Fondazione...