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Adaptive Responses to Monotherapy in Head and Neck Cancer: Interventions for Rationale-Based Therapeutic Combinations
Sankar Jagadeeshan1, Manu Prasad1, Sandra Ortiz-Cuaran2
1The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
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.
Insights
Understanding head and neck cancer (HNC) resistance mechanisms is key. This review details intrinsic and extrinsic resistance to HNC monotherapies, guiding better treatment combinations.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Head and neck cancer (HNC) clinical trials often combine therapies, informed by resistance mechanisms to monotherapy.
- Acquired resistance to HNC treatments can arise from tumor-intrinsic or tumor-microenvironment-extrinsic factors.
Purpose of the Study:
- To review intrinsic and extrinsic resistance mechanisms to FDA-approved HNC monotherapies.
- To elucidate how tumor cells and the tumor microenvironment (TME) adapt to radiation, chemotherapy, targeted therapy (cetuximab), and immunotherapy (PD-1 inhibitors).
Main Methods:
- Literature review of acquired resistance mechanisms in head and neck cancer.
- Analysis of adaptive responses to radiation, chemotherapy, cetuximab, and PD-1 inhibitors in HNC.
Main Results:
- Identified diverse intrinsic and extrinsic resistance mechanisms to HNC monotherapies.
- Described tumor cell and TME adaptations to selective pressure from various treatment modalities.
Conclusions:
- Monitoring treatment response is crucial for understanding resistance pathways in HNC.
- A rationale-based therapeutic strategy combining optimal drug combinations can improve HNC patient outcomes.
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