Influences of BRAF Inhibitors on the Immune Microenvironment and the Rationale for Combined Molecular and Immune Targeted Therapy

Sangeetha M. Reddy, Alexandre Reuben, Jennifer A. Wargo

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

The identification of key driver mutations in melanoma has led to the development of targeted therapies aimed at BRAF and MEK, but responses are often limited in duration. There is growing evidence that MAPK pathway activation impairs antitumor immunity and that targeting this pathway may enhance responses to immunotherapies. There is also evidence that immune mechanisms of resistance to targeted therapy exist, providing the rationale for combining targeted therapy with immunotherapy. Preclinical studies have demonstrated synergy in combining these strategies, and combination clinical trials are ongoing. It is, however, becoming clear that additional translational studies are needed to better understand toxicity, proper timing, and sequence of therapy, as well as the utility of multidrug regimens and effects of other targeted agents on antitumor immunity. Insights gained through translational research in preclinical models and clinical studies will provide mechanistic insight into therapeutic response and resistance and help devise rational strategies to enhance therapeutic responses.

Original languageEnglish (US)
Article number42
JournalCurrent Oncology Reports
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Fingerprint

Molecular Targeted Therapy
Immunotherapy
Immunity
Therapeutics
Translational Medical Research
Mitogen-Activated Protein Kinase Kinases
Antineoplastic Agents
Melanoma
Clinical Trials
Mutation

Keywords

  • BRAF
  • Checkpoint blockade
  • Combination therapy
  • MEK
  • Melanoma
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Influences of BRAF Inhibitors on the Immune Microenvironment and the Rationale for Combined Molecular and Immune Targeted Therapy. / Reddy, Sangeetha M.; Reuben, Alexandre; Wargo, Jennifer A.

In: Current Oncology Reports, Vol. 18, No. 7, 42, 01.07.2016.

Research output: Contribution to journalReview article

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