Tumor cell killing by cell cycle checkpoint abrogation combined with inhibition of the classical mitogen activated protein (map) kinase pathway

摘要

The present invention provides a method for treating cancer by promoting apoptosis and reducing clonogenic survival of cancer cells. The method encompasses co-administering 1) a cell cycle checkpoint abrogation agent (for example, UCN-01 or caffeine) and 2) an inhibitor of a compensatory cytoprotective pathway, such as an agent that inhibits the MEK 1/2 pathway (e.g. PD98059, U0126, or PD184352) or an agent that inhibits the PI 3 pathway (e.g. LIY294002 or wortmanin). In addition, because the co-administration step also radiosensitizes cancer cells, the method additionally encompasses the administration of radiation to further reduce clonogenic survival of cancer cells. The method promotes apoptosis and reduces clonogenic survival in many types of cancer cells, including leukemia cells, prostate cancer cells, breast cancer cells, myeloma cells, and lymphoma cells.