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The Adaptability of Chromosomal Instability in Cancer Therapy and Resistance

Vinicio Carloni1, Elisa Morganti1, Andrea Galli1

  • 1Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50121 Florence, Italy.

International Journal of Molecular Sciences
|January 8, 2023
PubMed

Insights

Chromosomal instability, driven by DNA damage and response, fuels cancer evolution and therapeutic resistance. Understanding these processes reveals vulnerabilities for developing new cancer treatments.

Area of Science:

  • Genetics and Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Chromosomal structural variations are a primary driver of DNA damage and response, hallmarks of chromosomal instability.
  • Cancer cells exploit DNA damage and response mechanisms for evolutionary adaptation under therapeutic pressure.
  • Recent research highlights vulnerabilities in DNA damage response, chromatin, and inflammation in cancer progression.

Purpose of the Study:

  • To investigate the role of DNA damage and chromosomal instability in cancer initiation and progression.
  • To identify vulnerabilities associated with aberrant DNA damage response, chromatin alterations, and inflammation.
  • To explore how understanding these vulnerabilities can inform treatment strategies and overcome therapy resistance.

Main Methods:

  • Analysis of DNA damage and response pathways in cancer cells.
  • Investigation of chromosomal structural variations and their impact.
  • Evaluation of chromatin modifications and inflammatory markers in cancer.
  • Correlation of DNA damage response with therapeutic outcomes.

Main Results:

  • Chromosomal instability is intrinsically linked to DNA damage and response, crucial for cancer evolution.
  • Cancer cells utilize DNA damage/response as an adaptive mechanism against therapy.
  • Aberrant DNA damage response, chromatin changes, and inflammation represent key cancer vulnerabilities.

Conclusions:

  • Understanding cancer's reliance on DNA damage and response mechanisms is vital.
  • Targeting vulnerabilities in DNA damage response, chromatin, and inflammation can lead to novel cancer therapies.
  • This knowledge aids in predicting treatment response and preventing tumor resistance.
Keywords:
DNA damageDNA damage responseepigenetic changesimmune evasionimmunotherapy

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