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Is Cell Death a Critical End Point for Anticancer Therapies or Is Cytostasis Sufficient?

Authors' Affiliations: ¹ Medical Oncology Department of the Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France and ² Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland

Requests for reprints: Olivier Rixe, Hôpital Pitié-Salpêtrière, Service d'Oncologie Médicale, 47, Bd de l'Hôpital, 75013 Paris, France. Phone: 33-1421-60471; E-mail: olivier.rixe{at}yahoo.com.

Abstract

Since the discovery of conventional chemotherapy and the development of new target-based agents, the importance of cytostasis in anticancer activity has been debated. This review examines the relative importance of both cytostasis and cytotoxicity based on both preclinical data and clinical reports. Several limitations of our basic and clinical methods to evaluate cytostasis and cytotoxicity will be highlighted. Molecular mechanisms of cytostasis will be analyzed, including interference with the cell cycle as well as putative links with necrosis and autophagy. Finally, we will cite evidence that most older and newer compounds are both cytostatic and cytotoxic. The relative role of cytostasis and cytotoxicity on future drug screening and clinical development will be explored.

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