Is cell death a critical end point for anticancer therapies or is cytostasis sufficient?
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.
Rixe
Olivier
O
Medical Oncology Department of the Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France. olivier.rixe@yahoo.com
Fojo
Tito
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002986:Clinical Trials as Topic; D054697:Cytostatic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D054697:Cytostatic Agents