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Scientists at the Indian Association for the Cultivation of Science (IACS) in Kolkata have discovered a new target for killing cancer cells using human breast cancer cells.
This target is related to how cancer cells regulate DNA repair during cell division, offering potential for new therapies.
The findings were published in The EMBO Journal.
The study suggests that developing novel anti-cancer therapeutics could be possible by targeting two key molecules: the CDK1 protein and the TDP1 enzyme.
Current anti-cancer drugs (camptothecin, topotecan, irinotecan) target an enzyme (Top1) involved in DNA replication and transcription.
Top1 plays a critical role in mitosis by relaxing DNA supercoils generated during transcription in condensed chromosomes.
Top1 is an enzyme found in all higher organisms that maintains DNA structure during replication and transcription.
Drugs targeting Top1 disrupt its activity, leading to the death of many cells, including cancer cells.
However, cancer cells can activate repair mechanisms using the TDP1 protein, which counteracts the effects of the drugs.
Understanding the overexpression of DNA repair proteins like Top1, TDP1, or CDK1 in cancers provides insights into tumor biology.
This knowledge can aid in diagnosing and predicting cancer outcomes and guide the development of targeted and personalized treatment strategies.
The study suggests that targeting another protein, CDK1, can disrupt the Top1-mediated DNA damage repair process.
This disruption can kill cancer cells by causing chromosomal instability and halting cell division.
CDK1 inhibitors (avotaciclib, alvocidib, roniciclib, riviciclib, dinaciclib) are currently in various stages of clinical trials.
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