Adaptive Responses to Monotherapy in Head and Neck Cancer: Interventions for Rationale-Based Therapeutic Combinations

Sankar Jagadeeshan, Manu Prasad, Sandra Ortiz-Cuaran, Vincent Gregoire, Pierre Saintigny, Moshe Elkabets

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Most Phase II and III clinical trials in head and neck cancer (HNC) combine two or more treatment modalities, which are based, in part, on knowledge of the molecular mechanisms of innate and acquired resistance to monotherapy. In this review, we describe the range of tumor-cell autonomously derived (intrinsic) and tumor-microenvironment-derived (extrinsic) acquired-resistance mechanisms to various FDA-approved monotherapies for HNC. Specifically, we describe how tumor cells and the tumor microenvironment (TME) respond to radiation, chemotherapy, targeted therapy (cetuximab), and immunotherapies [programmed cell death 1 (PD-1) inhibitors] and adapt to the selective pressure of these monotherapies. Due to the diversity of adaptive responses to monotherapy, monitoring the response to treatment in patients is critical to understand the path that leads to resistance and to guide the optimal therapeutic drug combinations in the clinical setting. We envisage that applying such a rationale-based therapeutic strategy will improve treatment efficacy in HNC patients.

Original languageEnglish
Pages (from-to)365-390
Number of pages26
JournalTrends in Cancer
Volume5
Issue number6
DOIs
StatePublished - 1 Jun 2019

Keywords

  • cellular signaling
  • head and neck
  • monotherapy
  • therapeutic resistance
  • tumor immunity
  • tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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