CANCER CELLS & TREATMENT (Syllabus: GS Paper 3 – Sci and Tech)

Context: Using human breast cancer cells, a team of scientists at the Kolkata-based Indian Association for the Cultivation of Science (IACS) has discovered a new target (CDK1 protein and the TDP1 enzyme) for killing cancer cells, which can potentially lead to new therapies.

New Target for Killing Cancer Cells

• About: Developing novel anti-cancer therapeutics may become possible through a combinatorial targeting of two key molecules — the CDK1 protein and the TDP1 enzyme.
• Current Anti-Cancer Drug Targets: Camptothecin, topotecan, and irinotecan target the enzyme topoisomerase 1 (Top1), which is involved in DNA replication and transcription.
• Critical Role of Top1 in Mitosis: Top1 plays a critical role in mitosis by relaxing DNA supercoils generated during transcription, essential for proper chromosome function.

oTop1 is crucial for maintaining DNA structure during replication and transcription, and drugs targeting Top1 disrupt this process, killing many cells, including cancer cells.

• Research Focus: For the past decade, researchers at IACS have been investigating DNA repair pathways that provide resistance to camptothecin and its derivatives, aiming to develop targeted or personalized chemotherapy, especially for breast and ovarian cancers.
• Cancer Cells' Resistance Mechanisms: Cancer cells can activate repair mechanisms using the TDP1 protein, counteracting the effects of Top1-targeting drugs.
• Role of DNA Repair: Understanding the overexpression of DNA repair proteins like Top1, TDP1, or CDK1 in cancers can provide critical insights into tumor biology, aiding in diagnosis, prognosis, and the development of targeted therapies.
• Identification of TDP1 in DNA Repair: Researchers at IACS identified TDP1 as a key DNA repair protein in cancer cells, discovering that phosphorylation of TDP1 during cell division helps remove it from chromosomes.

• DNA Repair Process with CDK1 Inhibitors: Targeting the CDK1 protein can disrupt the Top1-mediated DNA repair process, potentially killing cancer cells by causing chromosomal instability and halting cell division.
• Synergistic Effects of Combining Inhibitors: Combining CDK1 inhibitors with Top1 inhibitors may enhance cancer treatment effectiveness by targeting different aspects of the cell cycle and DNA replication, making it harder for cancer cells to survive.