Pharmacologic inhibition of ataxia telangiectasia and Rad3-related (ATR) in the treatment of head and neck squamous cell carcinoma.

Journal Article (Journal Article;Review)

Head and neck squamous cell carcinoma (HNSCC) poses significant treatment challenges, with high recurrence rates for locally advanced disease despite aggressive therapy typically involving a combination of surgery, radiation therapy, and/or chemotherapy. HNSCCs commonly exhibit reduced or absent TP53 function due to genomic alterations or human papillomavirus (HPV) infection, leading to dependence on the S- and G2/M checkpoints for cell cycle regulation. Both of these checkpoints are activated by Ataxia Telangiectasia and Rad3-related (ATR), which tends to be overexpressed in HNSCC relative to adjacent normal tissues and represents a potentially promising therapeutic target, particularly in combination with other treatments. ATR is a DNA damage signaling kinase that is activated in response to replication stress and single-stranded DNA breaks, such as those induced by radiation therapy and certain chemotherapies. ATR kinase inhibitors are currently being investigated in several clinical trials as part of the management of locally advanced, recurrent, or metastatic HNSCC, along with other malignancies. In this review article, we summarize the rationale and preclinical data supporting incorporation of ATR inhibition into therapeutic regimens for HNSCC.

Full Text

Duke Authors

Cited Authors

  • Karukonda, P; Odhiambo, D; Mowery, YM

Published Date

  • February 2022

Published In

Volume / Issue

  • 61 / 2

Start / End Page

  • 225 - 238

PubMed ID

  • 34964992

Pubmed Central ID

  • PMC8799519

Electronic International Standard Serial Number (EISSN)

  • 1098-2744

Digital Object Identifier (DOI)

  • 10.1002/mc.23384


  • eng

Conference Location

  • United States