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

Journal of Translational Medicine

Meeting Report

Magdalena Thurin¹  David Stroncek²  Ignacio Melero³  Claus Garbe⁴  Martin Mihm⁵  Janis Taube⁶  Bastian Schilling⁷  Michael Davies⁸  Rolf Kiessling⁹  Giuseppe Masucci^1,10  Silvia Formenti^1,11  Soldano Ferrone^1,12  Roger Lo^1,13  Thomas F. Gajewski^1,14  Hassane M. Zarour^1,15  Alistair Cochran^1,16  Sandra Demaria^1,17  Giorgio Parmiani^1,18  Sara Tomei^1,19  Ena Wang^2,20  Michael Atkins^2,21  Samir Khleif^2,22  Jérôme Galon^2,23  Barbara Seliger^2,24  Alessandro Testori^2,25  Gennaro Ciliberto^2,26  Nicola Mozzillo^2,26  Paolo A. Ascierto^2,26  Gerardo Botti^2,26  Pedro Romero^2,27  Grant Mc Arthur^2,28  Francesco M. Marincola^2,29  Reinhard Dummer^3,30  Carlo Bifulco^3,31  Giuseppe Palmieri^3,32  Paul Lorigan^3,33  Igor Puzanov^3,34 

[1] Cancer Diagnosis Program, National Cancer Institute, NIH, Bethesda, MD, USA;Cell Processing Section, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, MD, USA;Centro de Investigación Médica Aplicada, and Clinica Universidad de Navarra, Pamplona, Navarra, Spain;Department of Dermatology, Center for Dermato Oncology, University of Tübingen, Tübingen, Germany;Department of Dermatology, Harvard Medical School, Boston, MA, USA;Department of Dermatology, Johns Hopkins University SOM, Baltimore, MD, USA;Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany;German Cancer Consortium (DKTK), Essen, Germany;Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden;Department of Oncology-Pathology, The Karolinska Hospital, Stockholm, Sweden;Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA;Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;Departments of Medicine and Molecular and Medical Pharmacology, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center at the University of California Los Angeles (UCLA), Los Angeles, CA, USA;Departments of Medicine and of Pathology, Immunology and Cancer Program, The University of Chicago Medicine, Chicago, IL, USA;Departments of Medicine, Immunology and Dermatology, University of Pittsburgh, Pittsburgh, PA, USA;Departments of Pathology and Laboratory Medicine and Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), John Wayne Cancer Institute, Santa Monica, CA, USA;Departments of Radiation Oncology and Pathology, Weill Cornell Medical College, New York, NY, USA;Division of Molecular Oncology, Unit of Bio-Immunotherapy of Solid Tumors, San Raffaele Institute, Milan, Italy;Division of Translational Medicine, Sidra Medical and Research Center, Doha, Qatar;Division of Translational Medicine, Sidra Medical and Research Centre, Doha, Qatar;Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA;Georgia Regents University Cancer Center, Georgia Regents University, Augusta, GA, USA;INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, Université Paris Descartes, Sorbonne Paris Cité, Centre de Recherche des Cordeliers, Paris, France;Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany;Istituto Europeo di Oncologia, Milan, Italy;Istituto Nazionale Tumori, Fondazione “G. Pascale”, Naples, Italy;Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland;Peter MacCallum Cancer Centre and University of Melbourne, Victoria, Australia;Sidra Medical and Research Centre, Doha, Qatar;Skin Cancer Unit, Department of Dermatology, University Hospital Zürich, 8091, Zurich, Switzerland;Translational Molecular Pathology, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA;Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy;University of Manchester/Christie NHS Foundation Trust, Manchester, UK;Vanderbilt University Medical Center, Nashville, TN, USA;

关键词: Melanoma;    BRAF Mutation;    Ipilimumab;    Vemurafenib;    Uveal Melanoma;   

DOI  :  10.1186/s12967-015-0736-1

 received in 2015-10-17, accepted in 2015-11-19,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Ascierto et al. 2015