WBR0160

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Oncology
Prompt	[[Prompt::A 14 year old boy presents to his physician for pain in his left thigh. X-ray shows a mass at the metadiaphysis of the left femur. Biopsy demonstrates anaplastic small blue, CD99 positive cells. Karyotype of the tumor reveals a t(11;22) translocation consistent with Ewing’s Sarcoma. The patient is placed on a chemotherapy regimen which includes an agent that intercalates between cytosine and guanine base pairs of DNA to inhibit RNA Polymerase. Which of the following is the most likely drug used in this patient?]]
Answer A	AnswerA::5-Fluorouracil
Answer A Explanation	[[AnswerAExp::5-U does not intercalate between DNA nucleotides, but rather acts as an anti-metabolite. 5-Fluorouracil (5-FU) is a pyrimidine analogue that inhibits thymidylate synthase. It is indicated for the treatment of a variety of adenocarcinomas and acts during S-phase of the cell cycle.]]
Answer B	AnswerB::Bleomycin
Answer B Explanation	AnswerBExp::Bleomycin is a chemotherapeutic used for the treatment of testicular tumors. Bleomycin acts by inducing oxygen free radical and DNA strand breaks. It is notorious for causing pulmonary fibrosis.
Answer C	AnswerC::Carmustine
Answer C Explanation	AnswerCExp::Carmustine is a derivative of mustard gas that acts as a chemotherapeutic by forming interstrand crosslinks in DNA, thereby preventing DNA replication and DNA transcription
Answer D	AnswerD::Dactinomycin
Answer D Explanation	AnswerDExp::Dactinomycin inhibits RNA polymerase by intercalating between Cytosine and Guanine nucleotides in DNA.
Answer E	AnswerE::Etoposide
Answer E Explanation	[[AnswerEExp::Etoposide is a topoisomerase inhibitor that causes DNA damage by inducing strand breaks. Etoposide is a cell-cycle specific chemotherapy that acts primarily during S and G2 phases. It is used in a variety of solid tumors including small cell lung carcinoma and other hematopoetic malignancies. It principal side effect is bone marrow supression.]]
Right Answer	RightAnswer::D
Explanation	[[Explanation::Ewing’s Sarcoma is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribs and clavicle (see Figure 1). Ewing’s sarcoma is most common in adolescent males. 95% percents of cases occur between the ages of 4 and 25 and there is a 5:1 male to female incidence ratio. Tumor cells have a characteristic small, round blue appearance. These cells are almost universally CD99 positive and 85% of cases are caused by a translocation between chromosomes 11 and 22. Ewing Sarcoma is treated with aggressive courses of multidrug chemotherapy. These regiments often include Dactinomycin. Dactinomycin inhibits RNA polymerase by intercalating between Cytosine and Guanine nucleotides in DNA. Cancer cells are highly transcriptionally active, and are thus susceptible to therapies that target RNA polymerase. However, dactinomycin can be quite toxic, as all cells require transcription. Its side effects include: bone marrow suppression, GI toxicity, alopecia and mouth ulcers. Distribution of Ewing Sarcoma Educational Objective: Dactinomycin inhibits RNA polymerase by intercalating between Cytosine and Guanine nucleotides in DNA. References: First Aid 2014 pages 402, 404]]
Approved	Approved::Yes
Keyword	WBRKeyword::Chemotherapy, WBRKeyword::Sarcoma, WBRKeyword::Cancer, WBRKeyword::Ewing’s sarcoma
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::