Molecular cancer therapeutics: recent progress and targets in drug resistance.
Recent progress in development of molecular cancer therapeutics revealed new types of antitumor drugs, such as Herceptin, Gleevec, and Iressa as potent therapeutics for each specific tumor. We have been working on molecular cancer therapeutics, and in particular, those related to drug resistance, Here, I describe several resistance mechanisms, including apoptosis regulation, cellular stress response and cellular survival signals which have show close relevance to drug resistance. P-glycoprotein (P-gp) is the key molecule in multidrug resistance (MDR) and a good target for chemotherapy. Proteasome is involved in the resistance mechanism to topo II-targeted chemotherapy in solid tumors. Apoptosis program in tumor cells plays a critical role in chemotherapy-induced tumor cell killing, and the blockade of the apoptosis-inducing pathway could be another mechanism for drug resistance. Glyoxalase I is a molecule involved in apoptosis resistance mechanism in tumors. Survival (antiapoptosis) signals are the good targets for various antitumor drugs to overcome innate drug resistance. Our present studies provide novel targets for effective molecular cancer therapeutics in future.
Tsuruo
Takashi
T
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000502:physiology; D004351:Drug Resistance; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D008967:Molecular Biology; D009097:Multienzyme Complexes / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009097:Multienzyme Complexes; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D007791:Lactoylglutathione Lyase