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. 2015 Nov 30:13:374.
doi: 10.1186/s12967-015-0736-1.

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014

Paolo A Ascierto  1 , Michael Atkins  2 , Carlo Bifulco  3 , Gerardo Botti  4 , Alistair Cochran  5 , Michael Davies  6 , Sandra Demaria  7 , Reinhard Dummer  8 , Soldano Ferrone  9 , Silvia Formenti  10 , Thomas F Gajewski  11 , Claus Garbe  12 , Samir Khleif  13 , Rolf Kiessling  14 , Roger Lo  15 , Paul Lorigan  16 , Grant Mc Arthur  17 , Giuseppe Masucci  18 , Ignacio Melero  19 , Martin Mihm  20 , Giuseppe Palmieri  21 , Giorgio Parmiani  22 , Igor Puzanov  23 , Pedro Romero  24 , Bastian Schilling  25   26 , Barbara Seliger  27 , David Stroncek  28 , Janis Taube  29 , Sara Tomei  30 , Hassane M Zarour  31 , Alessandro Testori  32 , Ena Wang  33 , Jérôme Galon  34 , Gennaro Ciliberto  35 , Nicola Mozzillo  36 , Francesco M Marincola  37 , Magdalena Thurin  38
Affiliations

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014

Paolo A Ascierto et al. J Transl Med. .

Abstract

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.

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References

    1. Azimi F, Scolyer RA, Rumcheva P, et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol. 2012;30(21):2678–2683. doi: 10.1200/JCO.2011.37.8539. - DOI - PubMed
    1. Marchand M, van Baren N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 1999;80(2):219–230. doi: 10.1002/(SICI)1097-0215(19990118)80:2<219::AID-IJC10>3.0.CO;2-S. - DOI - PubMed
    1. Connerotte T, Van Pel A, Godelaine D, et al. Functions of anti-MAGE T-cells induced in melanoma patients under different vaccination modalities. Cancer Res. 2008;68(10):3931–3940. doi: 10.1158/0008-5472.CAN-07-5898. - DOI - PubMed
    1. Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364(22):2119–2127. doi: 10.1056/NEJMoa1012863. - DOI - PMC - PubMed
    1. Oshita C, Takikawa M, Kume A, et al. Dendritic cell-based vaccination in metastatic melanoma patients: phase II clinical trial. Oncol Rep. 2012;28(4):1131–1138. - PMC - PubMed

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