Neoplasia: cell cycle control and Rb: practice question

A Pathology 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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Pathology · Neoplasia: cell cycle control and Rb

Sample item

A 55-year-old woman with hormone receptor-positive metastatic breast cancer is started on palbociclib, a CDK4/6 inhibitor. What is the intended effect at the level of the cell cycle?

AReleasing E2F from Rb to push cells into S phaseBBlocking MDM2 so that p53 accumulatesCActivating p53 to induce apoptosis through BAXDKeeping Rb hypophosphorylated and bound to E2F, causing G1 arrest

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

The answer and the reasoning

D. Keeping Rb hypophosphorylated and bound to E2F, causing G1 arrest

Cyclin D with CDK4 or CDK6 phosphorylates Rb in G1, which releases E2F transcription factors and allows entry to S phase. By inhibiting these kinases, palbociclib keeps Rb in its active hypophosphorylated state bound to E2F, so cells arrest in G1. It only works in tumours that still have intact Rb.

Option by option

A. Releasing E2F from Rb to push cells into S phase
Release of E2F from Rb is the effect of CDK activity, which the drug is blocking.
B. Blocking MDM2 so that p53 accumulates
MDM2 inhibition is a different strategy, and the drug targets CDK4/6 and not the p53 pathway.
C. Activating p53 to induce apoptosis through BAX
The drug does not act through p53 or BAX, and apoptosis is not its primary mechanism.
D. Keeping Rb hypophosphorylated and bound to E2F, causing G1 arrest (correct)
Preventing Rb phosphorylation holds E2F in check and arrests cells in G1.

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 Pathology question

What is the answer to this Pathology question?

The best answer is D, Keeping Rb hypophosphorylated and bound to E2F, causing G1 arrest. Cyclin D with CDK4 or CDK6 phosphorylates Rb in G1, which releases E2F transcription factors and allows entry to S phase.

Why is "Releasing E2F from Rb to push cells into S phase" not the answer?

Release of E2F from Rb is the effect of CDK activity, which the drug is blocking.

Why is "Blocking MDM2 so that p53 accumulates" not the answer?

MDM2 inhibition is a different strategy, and the drug targets CDK4/6 and not the p53 pathway.

Why is "Activating p53 to induce apoptosis through BAX" not the answer?

The drug does not act through p53 or BAX, and apoptosis is not its primary mechanism.

What concept does this question test?

It tests Neoplasia: cell cycle control and Rb in Pathology. By inhibiting these kinases, palbociclib keeps Rb in its active hypophosphorylated state bound to E2F, so cells arrest in G1. It only works in tumours that still have intact Rb.

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 Neoplasia: cell cycle control and Rb?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology 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.