[Drug resistance mediated by survival- and growth-promoting signaling pathways].
The serine/threonine kinases, Akt and Pim, are key molecules for cell signaling downstream of growth factors, cytokines and other stimuli. Akt and Pim kinases regulate cellular processes that are associated with the aggressiveness of a number of different cancers. They protect cells from undergoing apoptosis and promote cell growth by phosphorylating their downstream substrates, which lead to the occurrence of resistance to anti-cancer drugs and radiation. Activation of Akt and Pim by transfecting their expression plasmids or by modulating their regulators attenuated the cytotoxic effects of anti-tumor drugs. Thus, the pathways are attractive targets for enhancing the sensitivity to and overcoming resistance to anti-cancer drugs. Recently, several small molecular inhibitors targeting the components of the Akt and Pim signaling pathways have been developed, and some inhibitors have already entered clinical trials. Further, some interesting associated proteins and substrates of the pathways have been identified. In future, new therapy targeting Akt and Pim signaling pathways will be developed to selectively induce apoptosis in cancer cells and to overcome drug resistance.
Fujita
Naoya
N
Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt