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Breakthrough in Cancer Therapy
Context:
Researchers at the Kolkata-based Indian Association for the Cultivation of Science (IACS) have discovered a new target for cancer treatment. This finding could lead to more effective therapies for breast and ovarian cancers.
More on News:
- A new target for killing cancer cells regulating DNA repair during cell division has been identified. This target is crucial for understanding cancer cells’ response to topoisomerase 1 (Top1)- targeted chemotherapy.
- The study sheds light on how cancer cells sometimes develop resistance to chemotherapy by using their DNA repair mechanisms, including the role of TDP1 (Tyrosyl-DNA phosphodiesterase 1) in counteracting Top1 inhibitors.
Cancer
- Cancer is a condition where cells proliferate uncontrollably and spread to other areas of the body.
- It can start anywhere in the body and form tumours, which can be malignant (cancerous) or benign (non-cancerous).
- Cancer cells differ from normal cells in that they grow without proper signals, ignore stop signals, invade other tissues, promote blood vessel growth, evade the immune system, and have abnormal chromosomes.
- It develops from genetic changes in proto-oncogenes, tumour suppressor genes, and DNA repair genes.
- It can spread to other body parts through metastasis and may affect various organs and tissues, leading to different types such as carcinomas, sarcomas, leukemias, lymphomas, melanomas, and brain tumours.
Key Highlights:
- The study proposes a combinatorial targeting strategy involving two key molecules:
- Top1: An enzyme critical for DNA replication and transcription, targeted by current drugs like camptothecin, topotecan, and irinotecan.
- CDK1 (Cyclin-Dependent Kinase 1): A protein that, when inhibited, can disrupt the DNA repair process mediated by TDP1, leading to increased cancer cell death.
- CDK1 directly regulates TDP1 through chemical modifications, helping repair DNA breaks caused by camptothecin.
- Inhibiting CDK1 could enhance the effectiveness of Top1 inhibitors by causing chromosomal instability and halting cell division.
- CDK1 inhibitors such as avotaciclib, alvocidib, roniciclib, riviciclib, and dinaciclib are in various stages of clinical trials.
- Combining these inhibitors with Top1 inhibitors could potentially improve treatment outcomes by overcoming resistance mechanisms and targeting multiple aspects of cancer cell biology.
Implications:
- The study focused on human breast cancer cells, the combination of CDK1 and Top1 inhibitors may also benefit patients with other cancers, including ovarian, colorectal, and small-cell lung cancers (SCLC).
- Further research is needed to confirm these findings in lab settings and clinical trials, to advance personalised chemotherapy strategies to effectively target and kill cancer cells.