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

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.

Optimized anti–tumor effects of anthracyclines plus Vinca alkaloids using a novel, mechanism-based application schedule

“…[18][19][20] There is a long-lasting conceptual discussion of whether cytotoxic and cytostatic drugs should be combined. 33 The term "cytostatic drugs" has been used for drugs that act against tumor cells by inducing cell-cycle arrest. In our study, anthracyclines arrested the cell cycle and behaved like cytostatic drugs in the cell lines investigated.…”

Cellular injury evidenced by impedance technology and infrared microspectroscopy

“…Cytostatic and cytotoxic behaviour plays an important role in the progression of a drug into preclinical and clinical studies. Cytostatic drugs have been found to be metastases preventative and increase the survival rates of patients by delaying the time to disease progression [17]. Cytotoxic drugs, on the other hand, are less selective and the induced cell death could be more detrimental to the patient in terms of side effects.…”

“…Cytotoxic drugs, on the other hand, are less selective and the induced cell death could be more detrimental to the patient in terms of side effects. Rixe and Fojo (2007) found that a drug elicited either cytostatic or cytotoxic cellular responses depending on its active concentration [17].…”

In vitro genotoxicity assessment of the synthetic plant growth regulator, 1-naphthaleneacetamide

“…These data would be indicative of the cytotoxic and cytostatic effects of NAAm in human PBLs. Rixe and Fojo (2007) reported that cytostaticity may be defined as the inhibition of cell growth and/or proliferation, and this initial event can induce cell death if cytostasis is prolonged. Accordingly, in the present study, NAAm revealed a cytostatic effect for the 24 h exposure period without cytotoxicity, whereas this compound displayed both cytostatic and cytotoxic properties for 48 h treatment period due to prolonged exposure of the test substance on lymphocytes.…”