WBR0164
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| Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pharmacology |
| Sub Category | SubCategory::Oncology, SubCategory::Renal |
| Prompt | [[Prompt::A 3-year-old boy is brought to the pediatrician by his parents after they noticed blood in the child’s urine. Physical examination is remarkable for a palpable left flank mass. Biopsy of the mass reveals a mixed population of tubules, small round blue cells, and stroma. The child undergoes left nephrectomy and is placed on a course of adjuvant chemotherapy. Two weeks after the administration of chemotherapy, the child complains of dizziness, has trouble walking, and displays difficulty in dorsiflexion of both feet. What is the mechanism of action of the drugs most likely responsible for this patient's symptoms?]] |
| Answer A | AnswerA::Inhibits DNA and RNA synthesis by cross-linking DNA strands and causing strand breaks |
| Answer A Explanation | [[AnswerAExp::Cisplatin is a non-cell cycle specific alkylating agent. It inhibits DNA and RNA synthesis by cross-linking DNA strands, thereby causing strand breaks. It is indicated for genitourinary tumors and is extremely effective in testicular cancers. Cisplatin is associated with ototoxicity and nephrotoxicity.]] |
| Answer B | AnswerB::Inhibits DNA-dependent RNA polymerase by intercalating between cytosine and guanine nucleotides in DNA |
| Answer B Explanation | [[AnswerBExp::Dactinomycin inhibits DNA-dependent RNA polymerase by intercalating between cytosine and guanine nucleotides in DNA.]] |
| Answer C | AnswerC::Hyperstabilizes microtubules and inhibits the disassembly of the mitotic spindle |
| Answer C Explanation | [[AnswerCExp::Paclitaxel hyperstabilizes microtubules and inhibits the disassembly of the mitotic spindle, thereby arresting cell division in M-phase. It is primarily indicated for breast and ovarian carcinomas.]] |
| Answer D | AnswerD::Binds to the microtubular proteins of the mitotic spindle and results in microtubule crystallization |
| Answer D Explanation | [[AnswerDExp::Vinblastine is a member of the alkaloid family that inhibits microtubule assembly. Vinblastine binds to the microtubular proteins of the mitotic spindle and results in microtubule crystallization, mitotic arrest, and cell death. In contrast to vincristine, vinblastine is not usually indicated for Wilms' tumor. It is generally indicated for hematologic malignancies and testicular carcinoma. Unlike vincristine, neurotoxicity associated with vinblastine usually involves cranial nerve toxicity (change in voice, visual changes, and facial palsy), mental depression, dizziness, and seizures. Bone marrow suppression, severe jaw pain, and constipation are also significantly associated with vinblastine administration.]] |
| Answer E | AnswerE::Stimulates microtubule minus-end detachment by producing microtubule fragments |
| Answer E Explanation | [[AnswerEExp::Vincristine binds to tubulin dimers, thereby inhibiting the assembly of microtubulues and blocking cell progression through mitosis. Vincristine is indicated for a variety of cancers including Wilms’ tumor, choriocarcinoma, and leukemia. Vincristine administration is associated with peripheral neuropathy.]] |
| Right Answer | RightAnswer::E |
| Explanation | [[Explanation::Wilms' tumor or nephroblastoma is a rare embryonal cancer of the kidneys that typically affects children between the ages of 2 and 4. It is composed of blastemal, epithelial, and/or stromal cells. The pathogenesis is thought to involve mutations during embryogenesis that result in nephrogenic rests. Wilms' tumor may also be caused by a germline mutation of the WT1 gene that encodes a zinc finger transcription factor necessary for kidney development. In addtion, Wilms' tumor may be associated with WAGR syndrome (Wilms' tumor, Aniridia, Genitourinary anomalies, Retardation). Patients with Wilms' tumor often present with a large flank or abdominal mass that may be associated with hematuria, low-grade fever, anemia, or hypertension. The majority of cases are unilateral, but bilateral presentation may be present in approximately 5-10% of cases. The disease is often suspected on history and physical examination and confirmed by ultrasound followed by biopsy of the tumor. These tumors are very responsive to therapy with a 5 year survival of 90%. Wilms’ tumor is generally managed by surgical resection for unilateral tumors along with neoadjuvant or adjuvant chemotherapy and possibly radiation therapy in advanced cases. Chemotherapy often includes vincristine and dactinomycin. Doxorubicin, cyclophosphamide, etoposide, and carboplatin may be added for more advanced stages of cancer. Vincristine is a vinca alkaloid that binds to tubulin dimers, thereby inhibiting the assembly of microtubulues and blocking cell progression through mitosis. Vincristine is indicated for a variety of cancers including Wilms’ tumor, choriocarcinoma, and leukemia. The most prominent adverse event associated with vincristine is peripheral neurotoxicity, which may include arelfexia and peripheral neuropathy. The child in this vignette is exhibiting foot drop, a sign of vincristine-induced peripheral neuropathy. Educational Objective: Vincristine is a member of vinca alkaloid chemotherapy family. It is indicated for Wilms' tumor and is associated with peripheral neuropathy. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Chemotherapy, WBRKeyword::Cancer, WBRKeyword::Kidney, WBRKeyword::Wilms tumor, WBRKeyword::Mitosis, WBRKeyword::Peripheral neuropathy, WBRKeyword::Neuropathy, WBRKeyword::Side effect, WBRKeyword::Wilms' tumor, WBRKeyword::Wilms, WBRKeyword::Wilms', WBRKeyword::Vincristine, WBRKeyword::Adverse drug reaction, WBRKeyword::Adverse drug event, WBRKeyword::Adverse event, WBRKeyword::Vinca alkaloid, WBRKeyword::Vinca, WBRKeyword::Alkaloid |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |