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Published in: European Archives of Oto-Rhino-Laryngology 5/2020

01-05-2020 | Retinoblastoma | Review Article

CDK4/6 inhibitors in P16/HPV16-negative squamous cell carcinoma of the head and neck

Authors: Camelia Billard-Sandu, Yun-Gan Tao, Marie-Paule Sablin, Gabriela Dumitrescu, David Billard, Eric Deutsch

Published in: European Archives of Oto-Rhino-Laryngology | Issue 5/2020

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Abstract

Purpose

Addition of CDK4/6 inhibitors to a variety of established treatments in squamous cell carcinoma of the head and neck (SCCHN) has the potential to improve responses to other therapies and may help overcome treatment resistance. The SCCHN is a heterogeneous group of cancers of the oral cavity, the pharynx and the larynx with poor prognosis despite the aggressive multimodal therapies. In the past decade, significant advances were made in understanding of the molecular and genetic abnormalities leading to oncogenesis in SCCHN.

Recent findings

Besides EGFR targeting agents, antiangiogenic agents have been shown to produce antitumor activity in these tumors. The cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway regulates cellular proliferation by controlling the G1 to S cell cycle checkpoint. In SCCHN, the Rb pathway is frequently altered through amplification of CCND1 (cyclin D1) or deletion of CDKN2A (cyclin-dependent kinase inhibitor 2A) coding for p16INK4A, and thus promoting proliferation.

Summary

This article summarizes what we actually know of the place of CDK4/6 inhibitors in the therapeutic arsenal of SCCHN. CDK4/6 inhibitors could serve as a method to target these tumors, and both p16 loss and CCND1 amplification could be investigated as biomarkers.
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Metadata
Title
CDK4/6 inhibitors in P16/HPV16-negative squamous cell carcinoma of the head and neck
Authors
Camelia Billard-Sandu
Yun-Gan Tao
Marie-Paule Sablin
Gabriela Dumitrescu
David Billard
Eric Deutsch
Publication date
01-05-2020
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 5/2020
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-020-05891-2

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