WBR247

Author	PageAuthor::Gerald Chi
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Oncology
Prompt	[[Prompt::A new chemotherapeutic drug of unclear mechanism is under investigation. After treatment with the drug, hamster ovary cells are found to be arrested in metaphase. Further studies show that the drug and paclitaxel both bind to beta-tubulins and promote stabilization of microtubules. Which of the following drugs is most likely to have the same mode of action?]]
Answer A	AnswerA::Colchicine
Answer A Explanation	[[AnswerAExp::Incorrect Colchicine inhibits microtubule polymerization by binding to tubulin and functions as a mitotic poison. The mitosis-inhibiting function of colchicine has been used in karyotype studies. Arresting cells in metaphase by adding colchicine facilitates visualization of chromosomes under a light microscope. Apart from inhibiting mitosis, colchicine also inhibits neutrophil motility and produces an anti-inflammatory effect.]]
Answer B	AnswerB::Estramustine
Answer B Explanation	[[AnswerBExp::Incorrect Estramustine is made from coupling of estradiol and mustard through a carbamate link. However, estramustine has a weak DNA-alkylating action. In fact, it binds to beta-tubulin and microtubule-associated proteins and leads to microtubule disassembly. Estramustine is used primarily for the treatment of metastatic or locally advanced hormone refractory prostate cancer.]]
Answer C	AnswerC::Irinotecan
Answer C Explanation	[[AnswerCExp::Incorrect Irinotecan and topotecan are camptothecin analogs approved for clinical use in colorectal, ovarian, and small cell lung cancer. Camptothecins stabilize the normally transient DNA-topoisomerase I cleavable complex and cause an irreversible double-strand DNA break during replication. DNA topoisomerases are nuclear enzymes that reduce torsional stress in supercoiled DNA, allowing selected regions of DNA to become sufficiently untangled for replication, repair, and transcription. Camptothecin analogs inhibit the function of topoisomerase I, while anthracyclines, epipodophyllotoxins and acridines inhibit topoisomerase II.]]
Answer D	AnswerD::Ixabepilone
Answer D Explanation	[[AnswerDExp::Correct The epothilones resemble taxanes in that they bind to beta-tubulin and trigger microtubule nucleation and cell-cycle arrest at the G2-M interface. Epothilones bind to a site distinct from that of taxanes. Ixabepilone is approved for metastatic breast cancer treatment.]]
Answer E	AnswerE::Vincristine
Answer E Explanation	[[AnswerEExp::Incorrect The vinca alkaloids, in common with other drugs such as colchicine, podophyllotoxin, the taxanes, and the epothilones, block cells in mitosis. Their mechanism of action is to bind specifically to beta-tubulin and to block its polymerization with alpha-tubulin into microtubules.]]
Right Answer	RightAnswer::D
Explanation	[[Explanation::When hamster ovary cells are incubated with the investigational drug, cell division arrests in metaphase. In the absence of an intact mitotic spindle, duplicated chromosomes cannot correctly align along the division plate and may result in apoptosis. Paclitaxel differs from the vinca alkaloids and colchicine derivatives in that it binds to a different tubulin site and promotes rather than inhibits microtubule formation. The taxanes have a central role in the treating ovarian, breast, lung, gastrointestinal, genitourinary, and head and neck cancers. Educational Objective: References: ]]
Approved	Approved::No
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