#73 - THE WEEKLY USMLE TIMES
Highlights for the week of April 29, 2024
Welcome to this week’s issue of The USMLE Times… A special welcome to the 211 new members who have joined our community this week.
Here’s what’s on tap for issue #73 of the USMLE Times:
Question of the Week
Video lesson of the week
Tweet of the week
Links to this week’s training
Question deep-dive & breakdown
Let’s dive in!
A 66-year-old male recently diagnosed with advanced non-small cell lung cancer is being evaluated due to the sudden onset of gastrointestinal bleeding. The patient is currently undergoing treatment with a combination of paclitaxel, cisplatin, and bevacizumab. The medication most likely responsible for his current complaint works by targeting which of the following?
A. Alpha-4 integrin
B. Interleukin-6
C. Vascular endothelial growth factor
D. CD20
E. Epidermal growth factor receptor
F. Interleukin-12
G. Programmed death-ligand 1
The answer & question breakdown is at the bottom of the post.
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ANSWER + QUESTION BREAKDOWN
This question tests your knowledge of targeted cancer therapies and their mechanisms of action. The patient is undergoing treatment for non-small cell lung cancer with a combination of three drugs, one of which is likely causing GI bleeding. To answer this question, you need to understand the mechanisms of action of each drug and correlate it with the adverse effect mentioned.
ANSWER CHOICES:
ANSWER CHOICE A: Alpha-4 integrin
Drugs like natalizumab, which are used primarily to treat multiple sclerosis and Crohn's disease, target Alpha-4 integrin. These drugs inhibit leukocyte adhesion and migration, a mechanism not related to the typical treatment or side effects associated with NSCLC.
ANSWER CHOICE B: Interleukin-6
Drugs targeting IL-6, such as tocilizumab, are used to manage conditions like rheumatoid arthritis. They work by modulating immune responses but are not commonly used in treating NSCLC or associated with causing gastrointestinal bleeding in this context.
ANSWER CHOICE C: Vascular endothelial growth factor
Vascular endothelial growth factor (VEGF) is a signaling protein that stimulates angiogenesis. Bevacizumab, one of the drugs mentioned in the question, is used in cancer treatment to inhibit tumor blood supply—it is known to increase the risk of bleeding, making it a strong candidate for the answer.
ANSWER CHOICE D: CD20
Rituximab targets this B-cell antigen and is used to treat non-Hodgkin's lymphoma and chronic lymphocytic leukemia. However, it is not commonly used to treat lung cancer.
ANSWER CHOICE E: Epidermal growth factor receptor
Drugs that target EGFR, such as erlotinib or gefitinib, are used to treat certain types of NSCLC, particularly in patients with specific EGFR mutations. While these drugs can have gastrointestinal side effects, they are not typically linked with severe gastrointestinal bleeding.
ANSWER CHOICE F: Interleukin-12
IL-12 is a cytokine that activates T-cells and natural killer cells. It has been investigated as a potential cancer immunotherapy target but is not currently used in standard treatment regimens.
ANSWER CHOICE G: Programmed death-ligand 1
Drugs targeting the programmed death-ligand 1 (PD-L1), like pembrolizumab or atezolizumab, are checkpoint inhibitors used in cancer immunotherapy. These can have a range of immune-related side effects but are less commonly associated with gastrointestinal bleeding compared to anti-angiogenic agents like bevacizumab.
THE VERDICT: Bevacizumab, which targets VEGF, is used to limit the growth of blood vessels to tumors, effectively starving the cancer of nutrients and oxygen. However, by inhibiting VEGF, bevacizumab also compromises the integrity of blood vessel walls elsewhere in the body, increasing the risk of bleeding. In this clinical scenario, the sudden onset of gastrointestinal bleeding in a patient undergoing treatment with bevacizumab strongly suggests that the inhibition of VEGF is responsible for this adverse effect. This aligns with known side effects of bevacizumab, including a heightened risk of gastrointestinal perforation and bleeding.
FINAL ANSWER: C: Vascular endothelial growth factor
That’s it for issue #73 of The USMLE Times!
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