WBR0165

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Oncology, SubCategory::Reproductive
Prompt	[[Prompt::A 55 year old woman presents to her physician for persistent abdominal pain, bloating and unintentional weight loss of 10 pounds over the past two months. The physician performs a pelvic exam which reveals an adnexal mass. Serum CA-125 is positive. Abdominal CT reveals tumor that has invaded the omentum. When the therapeutic regimen is explained to the patient, the patient recognizes the name of one drug saying, “That one was on the stent my husband received”. What is the mechanism of action of the most likely drug?]]
Answer A	AnswerA::Inhibits microtubule polymerization
Answer A Explanation	AnswerAExp::'''Incorrect:''' Both vincristine and vinblastine bind to tubulin dimers, thereby inhibiting the assembly of microtubulues and blocking cell progression through mitosis.
Answer B	AnswerB::Inhibits microtubule depolymerization
Answer B Explanation	[[AnswerBExp::Correct: Paclitaxel hyperstabilizes microtubules and inhibits the disassembly of the mitotic spindle, thereby arresting dividing cells in M-phase. It is primarily used in breast and ovarian carcinomas. It is also used to coat coronary artery stents.]]
Answer C	AnswerC::Inhibits MTOR
Answer C Explanation	AnswerCExp::'''Incorrect:''' Sirolimus inhibits MTOR and is used for immunosuppression.
Answer D	AnswerD::Intercalates between Cytosine and Guanine
Answer D Explanation	AnswerDExp::'''Incorrect:''' Dactinomycin inhibits RNA polymerase by intercalating between Cytosine and Guanine nucleotides in DNA.
Answer E	AnswerE::Adds alkyl group to guanine N-7
Answer E Explanation	AnswerEExp::'''Incorrect:''' Cyclophosphamide is an alkylating agent that covalently cross-links guanine nucleotides at the N-7 nitrogen. While cyclophosphamide can be used to treat ovarian carcinoma, it is not used to coat drug-eluting stents.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Ovarian cancer often presents with vague symptoms such as bloating, pelvic pain, difficulty eating and frequent urination, that make the disease difficult to diagnose. Risk for ovarian cancer is increases with older age, nulliparity, and familial cancer syndromes caused by BRCA1 and BRCA2 mutations. In patients with high clinical suspicion for malignancy, a pelvic exam should be performed along with CA-125 measurement. Although CA-125 measurement suffers from low sensitivity for detection of early stage tumors, it may be useful to confirm diagnosis. In a post-menopausal woman with a palpable adnexal mass and CA-125 level greater than 65 U/mL, the positive predictive value is >95% for ovarian malignancy. Ovarianc For localized tumors, surgery is often sufficient for treatment of ovarian tumors. However, for more advanced tumors in which complete resection is not feasible, surgical “debulking” is often performed followed by intraperitoneal and IV chemotherapy. One of the drugs used to treat ovarian tumors is paclitaxel. Paclitaxel hyperstabilizes microtubules and inhibits the disassembly of the mitotic spindle, thereby arresting dividing cells in M-phase. Paciltaxel is also used to coat drug-eluting stents, which prevent restenosis by inhibiting intimal hyperplasia of vascular smooth muscle cells. Educational Objective: Paclitaxel is used to treat ovarian cancer and is used to coat drug-eluting stents. References: First Aid 2012 page 401 Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Chemotherapy, WBRKeyword::Stent, WBRKeyword::Ovarian cancer, WBRKeyword::Cancer, WBRKeyword::Mitosis
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