Expansion
G1, S, G2 and M, with checkpoints controlled by cyclins and p53
Expansion
- G1: growth and preparation. Contains the restriction point, after which the cell is committed
- S: DNA synthesis, doubling the genome
- G2: preparation for division, with a checkpoint for DNA damage
- M: mitosis, itself divided into prophase, metaphase, anaphase and telophase
- G0: quiescence, from which some cells never return
Control: cyclins and cyclin-dependent kinases drive progression; retinoblastoma protein restrains the G1 to S transition until phosphorylated; p53 arrests the cycle for repair or triggers apoptosis if damage is irreparable.
Loss of these brakes is central to cancer: p53 is mutated in more than half of human cancers, and Rb loss causes retinoblastoma and contributes to many others.
Cytotoxic drugs map onto the phases:
- S phase: antimetabolites (methotrexate, 5-fluorouracil, cytarabine), hydroxycarbamide
- M phase: vinca alkaloids (inhibit microtubule assembly) and taxanes (prevent disassembly)
- Phase non-specific: alkylating agents, platinum compounds
Rapidly cycling normal tissues, namely marrow, gut mucosa and hair follicles, explain the predictable toxicity profile of chemotherapy.