2002, Vol. 19, No. 1, Pages 21-41
Tumor-based rhythms of anticancer efficacy in experimental models
Teresa G. Granda
*
1 and Francis Lévi
*
2 1Hôpital Paul Brousse, INSERM EPI 0118 “Cancer Chronotherapeutics,” Université Paris XI, 14–16 Avenue Paul-Vaillant Couturier, Villejuif, 94800, France
2Hôpital Paul Brousse, INSERM EPI 0118 “Cancer Chronotherapeutics,” Université Paris XI, 14–16 Avenue Paul-Vaillant Couturier, Villejuif, 94800, France
Experimental tumor models constitute a prerequisite toward chronotherapy testing in cancer patients. Studies in experimental models are required to understand the relation between tumor rhythms and antitumor treatments efficacy. In healthy tissues, cell proliferation, and differentiation processes are regulated precisely and exhibit marked circadian rhythmicity. Experimental and
human tumors can retain circadian rhythms or display altered oscillations. Healthy tissues can also display rhythm modifications, possibly related to cancer stage. Cellular rhythms modulate the metabolism of cytotoxic agents and the cellular response to them; hence, they determine the chronopharmacology of anticancer drugs.
Circadian rhythms in host tolerability and/or cancer chemotherapy efficacy have been demonstrated with nontoxic doses of drugs in several experimental tumor models, while in other ones a circadian-time effect was only seen within a specific dose range. The usual
coupling between tolerability and efficacy rhythms of anticancer agents has resulted in significant improvement of their therapeutic index. Results of laboratory animal studies have been extrapolated to the design of clinical cancer therapy trials involving a chronobiological approach.
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