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Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer

Raghav Sundar1, Susana Miranda2, Daniel Nava Rodrigues2

  • 1The Institute of Cancer Research, London, UK; The Royal Marsden NHS Trust, London, UK; Department of Haematology-Oncology, National University Health System, Singapore.

Clinical Colorectal Cancer
|July 26, 2018
PubMed
Abstract

Insights

Loss of ataxia telangiectasia mutated (ATM) protein in colorectal cancer patients was linked to better survival with oxaliplatin therapy. ATM loss may guide future DNA repair-targeted treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ataxia telangiectasia mutated (ATM) protein is crucial for DNA repair signaling.
  • Loss of ATM function may enhance sensitivity to DNA damaging agents.
  • Investigating ATM expression in colorectal cancer (CRC) is important for understanding treatment response.

Purpose of the Study:

  • To analyze ATM protein expression in metastatic colorectal cancer (CRC) patients.
  • To correlate ATM loss with clinical outcomes and survival.
  • To evaluate ATM as a potential biomarker in CRC treatment.

Main Methods:

  • Analysis of clinical outcomes and tumor samples from 223 metastatic CRC patients (2012-2016).
  • Immunohistochemistry (IHC) used to assess ATM nuclear staining intensity.
  • ATM loss defined as a nuclear H-score ≤ 10.

Main Results:

  • ATM loss identified in 8% (17/223) of CRC samples, independent of RAS/RAF mutations.
  • ATM loss associated with improved overall survival after first-line oxaliplatin therapy (49 vs. 32 months).
  • No significant association found between ATM loss and irinotecan-based therapy or overall survival from diagnosis.

Conclusions:

  • ATM loss may serve as a predictive biomarker for oxaliplatin response in CRC.
  • ATM status could inform the development of novel DNA repair-targeting agents for CRC treatment.
Keywords:
ATMATRColorectal cancerDNA damage repairOxaliplatin

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