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Updated: Feb 11, 2026

Preparation of DNA-crosslinked Polyacrylamide Hydrogels
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The evolving role of DNA inter-strand crosslinks in chemotherapy

Halley B Rycenga1, David T Long1

  • 1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.

Current Opinion in Pharmacology
|April 22, 2018
PubMed

Insights

DNA crosslinking agents disrupt cancer cell growth by damaging DNA. Improving inter-strand crosslink (ICL) therapies could reduce toxicity and enhance cancer treatment effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • DNA crosslinking agents are chemotherapy drugs targeting rapidly dividing cancer cells.
  • These agents induce various DNA lesions, with inter-strand crosslinks (ICLs) being highly cytotoxic.
  • Current ICL-based therapies face limitations due to significant patient toxicity.

Purpose of the Study:

  • To review the development of clinical DNA crosslinking agents.
  • To explore cellular responses to different DNA lesions induced by these agents.
  • To identify future strategies for improving ICL-based chemotherapeutics.

Main Methods:

  • Review of existing clinical data and research on DNA crosslinking agents.
  • Analysis of cellular mechanisms involved in DNA damage and repair.
  • Examination of therapeutic strategies and their associated toxicities.

Main Results:

  • ICLs represent a potent but toxic DNA lesion, limiting therapeutic applications.
  • Cellular responses to DNA damage vary, influencing drug efficacy and toxicity.
  • Over 50 years of clinical use highlight challenges in optimizing ICL agent therapy.

Conclusions:

  • Further research into cellular responses is crucial for mitigating ICL agent toxicity.
  • Developing novel strategies to enhance the therapeutic index of ICL agents is essential.
  • Future advancements may lead to more effective and safer ICL-based cancer treatments.

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