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Updated: Dec 9, 2025
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach
Samuele Lodovichi1, Tiziana Cervelli2, Achille Pellicioli1
1Bioscience Department, University of Milan, Via Celoria 26, 20131 Milan, Italy.
Abstract:
Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome.
Insights
Cancer cells rely on DNA repair pathways for survival but are more susceptible to DNA damage. Inhibitors targeting these pathways offer a promising strategy for cancer treatment, especially when combined with existing therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Alterations in DNA repair pathways are key drivers of cancer development.
- Cancer cells exhibit increased susceptibility to DNA damage and depend on specific repair mechanisms for survival.
- Genomic sequencing advances have identified critical mutated genes in cancers, enabling targeted therapy development.
Purpose of the Study:
- To review principal DNA repair and cell cycle checkpoint pathways involved in cancer.
- To explore inhibitors targeting proteins within these pathways.
- To discuss the rationale for using these inhibitors alone or in combination with standard treatments.
Main Methods:
- Literature review of DNA repair pathways and associated cancer predispositions.
- Analysis of existing and developing inhibitors targeting DNA repair proteins.
- Examination of combination strategies with chemotherapy and radiotherapy.
Main Results:
- Specific DNA repair pathways are crucial for cancer cell survival.
- Numerous inhibitors targeting these pathways have been developed, showing efficacy.
- Combination therapies hold promise for improving patient clinical outcomes.
Conclusions:
- Targeting DNA repair pathways is a vital strategy in cancer therapy.
- Inhibitor combinations and adjuvant use with classic therapies can enhance treatment efficacy.
- Understanding pathway alterations is crucial for personalized cancer treatment.
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