Synergy of molecular targeted approaches and immunotherapy in melanoma: preclinical basis and clinical perspectives

Abstract

Introduction: Targeted therapy and immunotherapies are the novel pharmacologic treatment strategies for metastatic melanoma. BRAF and MEK inhibitors effectively block the hyperactivation of the MAPK pathway in BRAF mutant melanomas and also have several other effects on melanoma cells and on the immune response. The aim of this work is to discuss the rationale, evidence and perspectives of approaches combining target and immunotherapy against melanoma.

Areas covered: We first review the effects of BRAF and MEK inhibitors on melanoma cells and on the different components of the immune system. Afterwards, we summarize the results of the preclinical and clinical studies that have combined targeted therapy and immunotherapy for the treatment of melanoma.

Expert opinion: Clinical applications of immunotherapy strategies have recently changed the therapeutic mainstay for metastatic melanoma. Biologic and initial preclinical data support their integration with innovative molecular targeted therapies, opening enormous perspectives for researchers in the effort of finding a definitive cure. Main open challenges are the definition of reliable research models, assessment of effective schedules, safety issues and designing of personalized approaches.

Keywords:

• BRAF inhibitors
• immunotherapy
• melanoma
• targeted therapy

Declaration of interests

This manuscript was supported by grants from “Associazione Italiana Ricerca sul Cancro” (AIRC) MFAG 2014, N 15731and IG grant N 11515; “Associazione Italiana Ricerca sul Cancero-AIRC 5x1000”, Ricerca finalizzata Giovani Ricercatori (GR-2011–02349197). Fondo Ricerca locale 2013, Università degli Studi di Torino. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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