Log-kill hypothesis (Skipper)
A dose of chemotherapy kills a constant fraction of cancer cells, not a constant number, so each cycle removes the same proportion, which is why treatment continues after the tumour has disappeared from scans.
Overview
Howard Skipper, Frank Schabel and colleagues showed in mouse leukaemia that a given drug dose killed a fixed fraction of cells regardless of how many were present: first-order kinetics. The corollary is that curing a cancer means driving the count from billions to zero through repeated cycles, that a single surviving cell can regrow the tumour, and that treatment must continue past clinical remission. The hypothesis shaped curative chemotherapy in childhood leukaemia and Hodgkin lymphoma and remains the framework for cycle number, though solid tumours with Gompertzian kinetics and resistant clones follow it only approximately.
How it works
Cell kill per dose is a constant logarithm: surviving fraction S = exp(-k·dose) independent of the starting number, so cure requires enough cycles to pass below one cell.
- Explains why cycles continue after remission
- Basis of curative regimens in leukaemia and lymphoma
- Simple and testable in models
- Solid tumours deviate as growth fraction falls
- Ignores resistant subpopulations
- Assumes equal drug delivery to all cells
Latest papers
topQuery for this technology: (TITLE:"Log-kill hypothesis" OR ABSTRACT:"Log-kill hypothesis" OR TITLE:"Skipper" OR ABSTRACT:"Skipper") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Log-kill hypothesis (Skipper), not a curated reading list.
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