ATR Inhibition in Advanced Urothelial Carcinoma

Clin Genitourin Cancer. 2023 Apr;21(2):203-207. doi: 10.1016/j.clgc.2022.10.016. Epub 2022 Nov 4.

Abstract

The ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase 1 (CHK1) pathway is intricately involved in protecting the integrity of the human genome by suppressing replication stress and repairing DNA damage. ATR is a promising therapeutic target in cancer cells because its inhibition could lead to an accumulation of damaged DNA preventing further replication and division. ATR inhibition is being studied in multiple types of cancer, including advanced urothelial carcinoma where there remains an unmet need for novel therapies to improve outcomes. Herein, we review preclinical and clinical data evaluating 4 ATR inhibitors as monotherapy or in combination with chemotherapy. The scope of this review is focused on contemporary studies evaluating the application of this novel therapy in advanced urothelial carcinoma.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Ataxia Telangiectasia*
  • Carcinoma, Transitional Cell* / drug therapy
  • Carcinoma, Transitional Cell* / genetics
  • DNA Damage
  • Humans
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / genetics

Substances

  • Ataxia Telangiectasia Mutated Proteins
  • ATR protein, human