Tumor senescence as a determinant of drug response in vivo.

It has become apparent in the last few years that induction of apoptosis is insufficient to account for the therapeutic effect of anticancer agents. Chemotherapy and radiation induce two other antiproliferative responses in tumor cells, cell death through mitotic catastrophe and terminal growth arrest through the program of senescence. Different types of tumor cells were found to develop the senescent phenotype upon drug treatment in vitro and in vivo. Cell culture studies demonstrated that this phenotype marks tumor cells that survive drug exposure but lose the ability to proliferate, and that such cells activate multiple growth-inhibitory genes. A recent study demonstrated that senescence, along with apoptosis, is a key determinant of in vivo response to chemotherapy in a transgenic mouse model of B-cell lymphoma. This review discusses the results of the latter study, as well as the differences between the genetic determinants of treatment-induced senescence in murine lymphoma and in human solid tumor cells.