Anticancer drugs: imatinib resistance: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Anticancer drugs: imatinib resistance

Sample item

A 50-year-old man with chronic myeloid leukaemia initially responded to imatinib, but BCR-ABL transcripts are now rising and sequencing shows a T315I mutation in the kinase domain. Which drug is active against this mutation?

ADasatinibBNilotinibCPonatinibDA higher dose of imatinib

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

C. Ponatinib

The T315I gatekeeper mutation blocks binding of imatinib, dasatinib, nilotinib and bosutinib. Ponatinib was designed to inhibit it, and asciminib (an allosteric inhibitor) is also active against it. Ponatinib carries a risk of arterial occlusive events and hypertension.

Option by option

A. Dasatinib
Dasatinib is ineffective against T315I.
B. Nilotinib
Nilotinib is ineffective against T315I.
C. Ponatinib (correct)
Correct. Ponatinib binds BCR-ABL despite the gatekeeper change.
D. A higher dose of imatinib
Higher imatinib doses cannot overcome the gatekeeper mutation.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is C, Ponatinib. The T315I gatekeeper mutation blocks binding of imatinib, dasatinib, nilotinib and bosutinib.

Why is "Dasatinib" not the answer?

Dasatinib is ineffective against T315I.

Why is "Nilotinib" not the answer?

Nilotinib is ineffective against T315I.

Why is "A higher dose of imatinib" not the answer?

Higher imatinib doses cannot overcome the gatekeeper mutation.

What concept does this question test?

It tests Anticancer drugs: imatinib resistance in Pharmacology. Ponatinib was designed to inhibit it, and asciminib (an allosteric inhibitor) is also active against it. Ponatinib carries a risk of arterial occlusive events and hypertension.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Anticancer drugs: imatinib resistance?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.