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Updated: Sep 13, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug

Xue Gong1, Yongzhao Zhou1, Yi Deng1

  • 1Integrated Care Management Center, Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, China.

Current Oncology (Toronto, Ont.)
|July 25, 2025
PubMed

Insights

This review explores the DNA damage response (DDR) in non-small cell lung cancer (NSCLC), focusing on regulatory networks that impact treatment resistance. Understanding these pathways can reveal new therapeutic targets to improve patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
  • Therapeutic resistance significantly limits treatment effectiveness in NSCLC patients.
  • The DNA damage response (DDR) is crucial for maintaining genomic stability and influences cancer therapy outcomes.

Purpose of the Study:

  • To comprehensively review the upstream and downstream pathways regulating DDR in NSCLC.
  • To identify key molecular regulators and signaling interactions involved in DDR.
  • To explore how DDR modulation contributes to therapeutic resistance and propose novel strategies.

Main Methods:

  • Literature review of existing research on DDR pathways in NSCLC.
  • Analysis of molecular regulators, signaling cascades, and feedback mechanisms.
  • Identification of potential biomarkers and therapeutic targets.

Main Results:

  • DDR dysregulation is a significant factor in NSCLC treatment resistance.
  • Focusing solely on direct DDR inhibitors overlooks broader regulatory networks.
  • Novel regulatory targets and biomarkers can be identified by analyzing these networks.

Conclusions:

  • Understanding the complex DDR regulatory network is crucial for overcoming therapeutic resistance in NSCLC.
  • Targeting upstream and downstream DDR modulators offers new therapeutic avenues.
  • This approach can bridge DDR dysregulation with precision oncology for improved patient outcomes.
Keywords:
DNA damage responsechemotherapydrug resistancehomologous recombinationnon-homologous end joiningnon-small cell lung cancerradiotherapytargeted therapy

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