Chemotherapy cell kill hypothesis

The cell-kill hypothesis states that the effects of antitumor drugs on tumor cell populations follow first-order kinetics. This means that the number of cells killed is proportional to the dose. Thus, chemotherapy follows an exponential or log-kill model in which a constant proportion, not a constant number, of cancer cells are killed. Ilieoretically. the fractional reductions possible with cancer chemotherapy can never reduce tumor populations to zero. Complete er ica-tion requires another effect, such as the immune response. A modified form of the first-order log-kill hypothesis holds that tumor regressions produced by chemotherapy are de-.scribed by the relative growth fraction present in the tumor at the lime of treatment This idea is consistent with the finding that very small and very large tumors are less responsive than tumors of intermediate size. ... 

Under certain conditions, the Gompertzian tumor model provides an accurate barometer for tumor growth in vivo. However, deviations occur over time due to selection and expansion sub-clones that are chemo-resistant. Skipper s Cell Kill Hypothesis is based on the notion that chemotherapy will lead first-order cell kill kinetics. Therefore, each administration of chemotherapy will produce tiie same fraction of tumor cell death. In theory, it is believed that a log-cell drop of 9 to 11 orders of magnitude is required for tumor eradication. Clinically this scenario is complicated by the chemosen-sitivity of normal tissue and tumor, pharmacokinetic hetereogeneity of patients, and tumor heterogeneity. 

Log-kill hypothesis A concept used in cancer chemotherapy to mean that anticancer drugs kill a fixed proportion of a tumor cell population, not a fixed number of tumor cells. For example, a 1-log-kill will decrease a tumor cell population by one order of magnitude, ie, 90% of the cells will be eradicated... 

---