78. As topoisomerases play an important role during replication, a large number of anticancer drugs have been developed that inhibit the activity of these enzymes. Which of the following statements is NOT true about topoisomerases as a potential anticancer drug target ?

(1) AS cancer cells are rapidly growing cells. They contain higher level of topoisomerases.

(2) The transient DNA breaks created by topotsomerases are usually converted to permanent breaks in the genome in the presence of topoisomerase targeted drugs.
(3) As cancer cells often have impaired DNA repair pathways. they are more susceptible-towards topoisomerase targeted drugs.

(4) The drugs which specifically target topoisomerases, usually do not affect normal fast growing cells.

Overview of Topoisomerases and Anticancer Drugs

Topoisomerases are essential enzymes that manage DNA topology during replication and transcription by creating transient DNA breaks. Anticancer drugs targeting topoisomerases exploit these transient breaks, stabilizing enzyme-DNA complexes and converting temporary breaks into permanent DNA damage, leading to cancer cell death.

Evaluating Each Statement

1. Cancer cells have higher levels of topoisomerases due to rapid growth.

   • True. Rapidly proliferating cancer cells express elevated levels of topoisomerases, making these enzymes effective drug targets.

2. Topoisomerase-targeted drugs convert transient DNA breaks into permanent genome breaks.

   • True. Drugs like camptothecin (Topoisomerase I inhibitors) and etoposide (Topoisomerase II inhibitors) stabilize cleavage complexes, preventing DNA re-ligation and causing permanent double-strand breaks.

3. Cancer cells with impaired DNA repair pathways are more susceptible to topoisomerase-targeted drugs.

   • True. Defective DNA repair mechanisms in cancer cells reduce their ability to resolve drug-induced DNA damage, increasing sensitivity.

4. Drugs targeting topoisomerases usually do not affect normal fast-growing cells.

   • False. Topoisomerase inhibitors affect all rapidly dividing cells, including normal cells such as bone marrow, gastrointestinal lining, and hair follicles, leading to side effects like myelosuppression and mucositis.

Conclusion

The statement that is NOT true about topoisomerases as anticancer drug targets is:

(4) The drugs which specifically target topoisomerases, usually do not affect normal fast growing cells.

This is incorrect because topoisomerase inhibitors affect both cancerous and normal rapidly dividing cells, causing common chemotherapy side effects.

Keywords

topoisomerase inhibitors, anticancer drugs, DNA breaks, cancer cell susceptibility, DNA repair deficiency, chemotherapy side effects, camptothecin, etoposide, topoisomerase poisoning, normal cell toxicity

Correct answer:
(4) The drugs which specifically target topoisomerases, usually do not affect normal fast growing cells.