Article open access publication

Future perspectives in melanoma research “Melanoma Bridge”, Napoli, November 30th–3rd December 2016

Journal of Translational Medicine, Springer Nature, ISSN 1479-5876

Volume 15, 1, 2017

DOI:10.1186/s12967-017-1341-2, Dimensions: pub.1092735344, PMC: PMC5691855, PMID: 29145885,

Affiliations

Organisations

  1. (1) Istituto Nazionale Tumori di Napoli Fondazione “G. Pascale”, Via Mariano Semmola, 80131, Naples, Italy
  2. (2) Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy
  3. (3) Oncology & Hematology, St. Luke’s University Hospital and Temple University, Bethlehem, PA, USA
  4. (4) Istituti Fisioterapici Ospitalieri, grid.417520.5
  5. (5) Cornell University, grid.5386.8
  6. (6) University Hospital of Zurich, grid.412004.3
  7. (7) Institut Gustave Roussy, grid.14925.3b
  8. (8) Massachusetts General Hospital, grid.32224.35
  9. (9) University of Tübingen, grid.10392.39
  10. (10) Yale University, grid.47100.32
  11. (11) Augusta University, grid.410427.4
  12. (12) University of Chicago, grid.170205.1
  13. (13) The University of Texas MD Anderson Cancer Center, grid.240145.6
  14. (14) Memorial Sloan Kettering Cancer Center, grid.51462.34
  15. (15) Roswell Park Cancer Institute, grid.240614.5
  16. (16) UW Carbone Cancer Center, grid.412639.b
  17. (17) University of Wisconsin–Madison, grid.14003.36
  18. (18) Johns Hopkins University, grid.21107.35
  19. (19) Herlev Hospital, grid.411900.d, Capital Region
  20. (20) University of Copenhagen, grid.5254.6, KU
  21. (21) National Institutes of Health Clinical Center, grid.410305.3
  22. (22) University of Pittsburgh, grid.21925.3d
  23. (23) Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, MD, USA

Description

Major advances have been made in the treatment of cancer with targeted therapy and immunotherapy; several FDA-approved agents with associated improvement of 1-year survival rates became available for stage IV melanoma patients. Before 2010, the 1-year survival were quite low, at 30%; in 2011, the rise to nearly 50% in the setting of treatment with Ipilimumab, and rise to 70% with BRAF inhibitor monotherapy in 2013 was observed. Even more impressive are 1-year survival rates considering combination strategies with both targeted therapy and immunotherapy, now exceeding 80%. Can we improve response rates even further, and bring these therapies to more patients? In fact, despite these advances, responses are heterogeneous and are not always durable. There is a critical need to better understand who will benefit from therapy, as well as proper timing, sequence and combination of different therapeutic agents. How can we better understand responses to therapy and optimize treatment regimens? The key to better understanding therapy and to optimizing responses is with insights gained from responses to targeted therapy and immunotherapy through translational research in human samples. Combination therapies including chemotherapy, radiotherapy, targeted therapy, electrochemotherapy with immunotherapy agents such as Immune Checkpoint Blockers are under investigation but there is much room for improvement. Adoptive T cell therapy including tumor infiltrating lymphocytes and chimeric antigen receptor modified T cells therapy is also efficacious in metastatic melanoma and outcome enhancement seem likely by improved homing capacity of chemokine receptor transduced T cells. Tumor infiltrating lymphocytes therapy is also efficacious in metastatic melanoma and outcome enhancement seem likely by improved homing capacity of chemokine receptor transduced T cells. Understanding the mechanisms behind the development of acquired resistance and tests for biomarkers for treatment decisions are also under study and will offer new opportunities for more efficient combination therapies. Knowledge of immunologic features of the tumor microenvironment associated with response and resistance will improve the identification of patients who will derive the most benefit from monotherapy and might reveal additional immunologic determinants that could be targeted in combination with checkpoint blockade. The future of advanced melanoma needs to involve education and trials, biobanks with a focus on primary tumors, bioinformatics and empowerment of patients and clinicians.

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Times Cited: 10

Field Citation Ratio (FCR): 2.65

Relative Citation ratio (RCR): 0.45

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