Curriculum
Module 11 · 60 min
Cell Cycle & Checkpoints
CDKs, cyclins, restriction point — and the chemotherapy that exploits them.
CoreClinicalResearch
Topics
What this module covers
- 01G1/S restriction point: Rb-E2F switch
- 02Cyclin-CDK pairs across the cycle
- 03G1/S, intra-S, G2/M, and spindle-assembly checkpoints
- 04Mitosis: prophase → cytokinesis; cohesin/separase
- 05p53 as the gatekeeper; ATR/ATM signalling
- 06CDK4/6 inhibitors, Aurora and PLK inhibitors
Deep dives
Lesson sub-pages
Learning objectives
By the end of this module you will be able to
- L01Explain why CDK4/6 inhibitors are effective only in Rb-proficient breast cancers.
- L02Trace the spindle-assembly checkpoint signal from unattached kinetochore to APC/C inhibition.
- L03Predict which checkpoint is bypassed by a given oncogene/tumour-suppressor mutation.
Expected takeaways
What you should walk away believing
- →p53 is mutated in ~50% of human cancers — usually loss-of-function, sometimes gain-of-function neomorphs.
- →Synthetic lethality (e.g., PARP + BRCA-deficient) exploits checkpoint redundancy.
- →Most chemotherapy is, mechanistically, a checkpoint or mitotic catastrophe.
Core summary
At the Core level
The cell cycle is a decision machine: only divide if the genome is intact, the metabolism supports it, and external signals approve. Cyclin-CDK activity oscillates; checkpoints are quality gates that engage when problems are detected. Cancer is, in part, a failure of these gates.
Evidence-graded claims
Claims, scored A–F
A
CDK4/6 inhibitors require Rb for activity
Rb-null tumours are intrinsically resistant.
A
PARP inhibitors are selectively lethal in BRCA1/2-deficient cells
Synthetic lethality demonstrated and validated clinically.
C
Targeting WEE1 will be broadly effective in p53-deficient cancers
Adavosertib trials mixed; manageable but not transformative so far.
Quiz
Check your understanding
Q1. The restriction point is governed by:
Q2. Spindle-assembly checkpoint output is to:
Flashcards
Lock it in
1 / 3
Front
Three principal checkpoint kinases?
Click to flip
Suggested reading
Primary literature
- Cyclin-dependent kinases as therapeutic targets in cancer — Asghar et al., Nat Rev Drug Discov 2015 ↗