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Mechanisms of Drug Resistance in Cancer Therapy pp 129–143Cite as

Immunotolerance as a Mechanism of Resistance to Targeted Therapies in Melanoma

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 249))

Abstract

The therapy of metastatic melanoma (MM) was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in ≈40–50% of patients. Oncogenic BRAF promotes an immune-compromised tumour microenvironment (TME). Inhibition of MAPK pathway signaling with BRAF (BRAFi) and MEK inhibitors (MEKi) attenuates immune escape and increases the melanoma immunogenicity through multiple mechanisms, including elevation of melanoma antigen expression and improved T cell infiltration and function. These changes sustain the TME for response to immunotherapy. In this chapter we discuss preclinical and clinical data supporting the immunomodulating activities of targeted therapies, the immunotolerance as a mechanisms of resistance and highlight the rationale for novel combinations of targeted therapies and immunotherapies with the potential to significantly improve the future treatment of MM patients.

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Author information

Authors and Affiliations

  1. Unit of Medical Oncology, Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Piazza OMS 1, 24100, Bergamo, Italy

    Mario Mandalà

  2. Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy

    Daniela Massi

Authors
  1. Mario Mandalà
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  2. Daniela Massi
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Corresponding author

Correspondence to Mario Mandalà .

Editor information

Editors and Affiliations

  1. Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy

    Mario Mandalà

  2. Department of Oncology, INSERM Res Unit 932, Institut Curie, Paris Cedex 05, France

    Emanuela Romano

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Mandalà, M., Massi, D. (2017). Immunotolerance as a Mechanism of Resistance to Targeted Therapies in Melanoma. In: Mandalà, M., Romano, E. (eds) Mechanisms of Drug Resistance in Cancer Therapy. Handbook of Experimental Pharmacology, vol 249. Springer, Cham. https://doi.org/10.1007/164_2017_5

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