AP Syllabus focus:
‘Disruptions to regulatory pathways and checkpoints can lead to cancer, characterized by unregulated cell growth and tumor formation.’
Cancer results when the normal “stop-and-go” logic of the cell cycle is rewired. Mutations that override checkpoints or growth controls allow cells to divide when they shouldn’t, accumulating changes that promote tumor development.
From regulated division to uncontrolled proliferation
Healthy tissues balance cell division with cell death and differentiation using cell-cycle checkpoints and external growth signals. Cancer begins when disruptions make cells less dependent on these controls, leading to unregulated cell growth and ultimately tumor formation.
Cancer: A disease state in which cells proliferate uncontrollably due to disruptions in regulatory pathways and checkpoints, often forming tumors.
Key control points commonly affected in cancer include:
Diagram of the eukaryotic cell cycle highlighting the three major checkpoints (G1, G2/M, and M/spindle checkpoint). It summarizes what each checkpoint assesses—DNA integrity before S phase, completion/accuracy of DNA replication before mitosis, and proper kinetochore–spindle attachment before chromosome separation. Source
G1/S checkpoint (“restriction point”): commits a cell to DNA replication only if conditions are favorable.
G2/M checkpoint: blocks mitosis if DNA is damaged or incompletely replicated.
Spindle checkpoint: prevents chromosome separation until all chromosomes are correctly attached.
Gene-level disruptions that drive cancer
Cancer is typically a multistep process in which mutations accumulate in genes that control proliferation, checkpoint enforcement, and genome integrity.
Proto-oncogenes become oncogenes (accelerator stuck “on”)
Cells normally use proto-oncogenes to promote division only when appropriate (e.g., signal receptors, kinases, transcription factors). Mutations can create oncogenes that signal division even without proper cues.
Oncogene: A mutated or overexpressed gene that increases cell division or survival, contributing to uncontrolled proliferation.
Common oncogene-creating changes:
Flowchart summarizing multiple genetic routes by which proto-oncogenes can be converted into oncogenes. It emphasizes that different mutation types can produce a net gain of growth-promoting signaling, pushing cells toward checkpoint bypass and increased proliferation. Source
Gain-of-function point mutations that keep a signaling protein active
Gene amplification producing too much growth-promoting protein
Chromosomal rearrangements that place a growth gene under a strong promoter
These changes can reduce checkpoint effectiveness by pushing cells through the cycle despite warning signals.
Tumor suppressor genes are lost (brakes fail)
Tumor suppressor genes restrain the cell cycle, enforce checkpoints, and coordinate DNA damage responses.
Pathway map of the p53-dependent G1/S DNA-damage checkpoint, showing how DNA damage signaling activates p53 and downstream effectors that halt cell-cycle progression. This diagram helps connect “tumor suppressor loss” to the specific molecular logic behind checkpoint enforcement and mutation accumulation when the pathway is disrupted. Source
Cancer-promoting mutations often inactivate these genes, removing critical “brakes” on division.
Tumor suppressor gene: A gene whose normal function limits cell division or maintains genome stability; loss-of-function mutations increase cancer risk.
Typical outcomes of tumor suppressor loss:
Reduced ability to halt the cell cycle at checkpoints
Decreased DNA repair coordination, allowing mutations to persist
Increased probability that cells proceed through S phase and mitosis with errors
Unlike oncogenes, tumor suppressor disruptions often require loss of function in both gene copies in a cell lineage to fully remove restraint.
Checkpoint failure, mutation accumulation, and tumors
When checkpoints are weakened, cells can replicate damaged DNA or mis-segregate chromosomes. This creates genomic instability, accelerating the appearance of additional mutations that further promote unregulated growth.
Cancer-linked checkpoint disruption often produces:
Faster entry into S phase despite inadequate conditions
Persistence of cells with DNA damage
Increased chromosome number abnormalities (aneuploidy) from faulty mitosis
Over time, a clone of increasingly abnormal cells can expand into a tumor—a mass formed by excessive cell division. Tumors can remain localized (benign) or become invasive (malignant), but both reflect breakdown of normal cell-cycle regulation.
FAQ
Different genes control distinct barriers (growth signalling, checkpoints, genome stability).
A single mutation may increase division slightly, but additional mutations typically are needed to sustain uncontrolled proliferation and form a tumour.
An inherited mutation can provide a “first hit” in every cell.
Fewer additional somatic changes are then required in a particular cell lineage to disrupt regulation enough to permit tumour development.
Some viral proteins bind and inhibit key checkpoint regulators, pushing cells into S phase to copy viral genomes.
This inappropriate forcing of the cell cycle increases replication of damaged DNA and raises cancer risk.
Inflammation can raise cell turnover and expose tissues to reactive molecules that damage DNA.
More divisions plus more DNA damage increases opportunities for checkpoint-disrupting mutations to arise and expand.
Normal telomere shortening limits repeated division.
Many cancers maintain telomeres (often by reactivating telomerase), enabling more cell cycles and increasing the time window for accumulating regulatory disruptions.
Practice Questions
Explain how disruption of cell-cycle checkpoints can lead to tumour formation. (2 marks)
Checkpoints normally prevent progression when conditions are unsuitable or DNA is damaged (1)
Disruption allows continued division/uncontrolled proliferation, producing a mass of cells (tumour) (1)
A tissue sample shows rapid cell division. Sequencing finds either (A) a gain-of-function mutation in a growth-signalling protein or (B) a loss-of-function mutation in a checkpoint-control gene. Explain how each mutation type could contribute to cancer. (6 marks)
(A) Gain-of-function increases pro-division signalling even without external signals (1)
This drives more frequent entry into the cell cycle/through G1/S (1)
(B) Loss-of-function reduces checkpoint enforcement/cell-cycle arrest (1)
Damaged or unprepared cells proceed through replication/mitosis (1)
Both increase uncontrolled proliferation and tumour formation (1)
Both can promote further mutation accumulation due to continued cycling (1)
