TY - JOUR
T1 - Adaptive Responses to Monotherapy in Head and Neck Cancer
T2 - Interventions for Rationale-Based Therapeutic Combinations
AU - Jagadeeshan, Sankar
AU - Prasad, Manu
AU - Ortiz-Cuaran, Sandra
AU - Gregoire, Vincent
AU - Saintigny, Pierre
AU - Elkabets, Moshe
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - cellular signaling
KW - head and neck
KW - monotherapy
KW - therapeutic resistance
KW - tumor immunity
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85066149555&partnerID=8YFLogxK
U2 - 10.1016/j.trecan.2019.04.004
DO - 10.1016/j.trecan.2019.04.004
M3 - Review article
C2 - 31208698
AN - SCOPUS:85066149555
SN - 2405-8033
VL - 5
SP - 365
EP - 390
JO - Trends in Cancer
JF - Trends in Cancer
IS - 6
ER -
