ENTRY ko01524 Pathway NAME Platinum drug resistance DESCRIPTION Platinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. The mechanism of action of Platinum-based drugs involves covalent binding to purine DNA bases, which primarily leads to cellular apoptosis. Their clinical success is, however, limited due to severe side effects and intrinsic or acquired resistance to the treatment. Platinum resistance could arise from decreased drug influx, increased drug efflux, intracellular detoxification by glutathione, etc., decreased binding (e.g., due to high intracellular pH), increased DNA repair, decreased mismatch repair, defective apoptosis, and altered oncogene expression. CLASS Human Diseases; Drug resistance: antineoplastic PATHWAY_MAP ko01524 Platinum drug resistance REFERENCE PMID:14576837 AUTHORS Siddik ZH TITLE Cisplatin: mode of cytotoxic action and molecular basis of resistance. JOURNAL Oncogene 22:7265-79 (2003) DOI:10.1038/sj.onc.1206933 REFERENCE PMID:26184483 AUTHORS Martinez-Balibrea E, Martinez-Cardus A, Gines A, Ruiz de Porras V, Moutinho C, Layos L, Manzano JL, Buges C, Bystrup S, Esteller M, Abad A TITLE Tumor-Related Molecular Mechanisms of Oxaliplatin Resistance. JOURNAL Mol Cancer Ther 14:1767-76 (2015) DOI:10.1158/1535-7163.MCT-14-0636 REFERENCE PMID:17625587 AUTHORS Kelland L TITLE The resurgence of platinum-based cancer chemotherapy. JOURNAL Nat Rev Cancer 7:573-84 (2007) DOI:10.1038/nrc2167 REFERENCE PMID:26886018 AUTHORS Dilruba S, Kalayda GV TITLE Platinum-based drugs: past, present and future. JOURNAL Cancer Chemother Pharmacol 77:1103-24 (2016) DOI:10.1007/s00280-016-2976-z REFERENCE PMID:23442359 AUTHORS Lu HP, Chao CC TITLE Cancer cells acquire resistance to anticancer drugs: an update. JOURNAL Biomed J 35:464-72 (2012) DOI:10.4103/2319-4170.104411 REFERENCE PMID:24074238 AUTHORS Koster R, van Vugt MA, Timmer-Bosscha H, Gietema JA, de Jong S TITLE Unravelling mechanisms of cisplatin sensitivity and resistance in testicular cancer. JOURNAL Expert Rev Mol Med 15:e12 (2013) DOI:10.1017/erm.2013.13 REFERENCE PMID:21892204 AUTHORS Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G TITLE Molecular mechanisms of cisplatin resistance. JOURNAL Oncogene 31:1869-83 (2012) DOI:10.1038/onc.2011.384 REFERENCE PMID:17336087 AUTHORS Stewart DJ TITLE Mechanisms of resistance to cisplatin and carboplatin. JOURNAL Crit Rev Oncol Hematol 63:12-31 (2007) DOI:10.1016/j.critrevonc.2007.02.001 REFERENCE PMID:20647037 AUTHORS Koberle B, Tomicic MT, Usanova S, Kaina B TITLE Cisplatin resistance: preclinical findings and clinical implications. JOURNAL Biochim Biophys Acta 1806:172-82 (2010) DOI:10.1016/j.bbcan.2010.07.004 REFERENCE PMID:25546083 AUTHORS Jacobsen C, Honecker F TITLE Cisplatin resistance in germ cell tumours: models and mechanisms. JOURNAL Andrology 3:111-21 (2015) DOI:10.1111/andr.299 REFERENCE PMID:14609433 AUTHORS Fraser M, Leung B, Jahani-Asl A, Yan X, Thompson WE, Tsang BK TITLE Chemoresistance in human ovarian cancer: the role of apoptotic regulators. JOURNAL Reprod Biol Endocrinol 1:66 (2003) DOI:10.1186/1477-7827-1-66 REFERENCE AUTHORS Sousa GF, Wlodarczyk SR, Monteiro G. TITLE Carboplatin: molecular mechanisms of action associated with chemoresistance. JOURNAL Braz J Pharm Sci 50:693-701 (2014) DOI:10.1590/S1984-82502014000400004 REFERENCE PMID:24874729 AUTHORS Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, Castedo M, Kroemer G TITLE Systems biology of cisplatin resistance: past, present and future. JOURNAL Cell Death Dis 5:e1257 (2014) DOI:10.1038/cddis.2013.428 REFERENCE PMID:25058905 AUTHORS Dasari S, Tchounwou PB TITLE Cisplatin in cancer therapy: molecular mechanisms of action. JOURNAL Eur J Pharmacol 740:364-78 (2014) DOI:10.1016/j.ejphar.2014.07.025 REFERENCE PMID:20811617 AUTHORS Basu A, Krishnamurthy S TITLE Cellular responses to Cisplatin-induced DNA damage. JOURNAL J Nucleic Acids 2010:201367 (2010) DOI:10.4061/2010/201367 REFERENCE PMID:19190080 AUTHORS Chaudhry P, Asselin E TITLE Resistance to chemotherapy and hormone therapy in endometrial cancer. JOURNAL Endocr Relat Cancer 16:363-80 (2009) DOI:10.1677/ERC-08-0266 REFERENCE PMID:26867799 AUTHORS Li X, Lin Z, Zhang B, Guo L, Liu S, Li H, Zhang J, Ye Q TITLE beta-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1. JOURNAL Sci Rep 6:21010 (2016) DOI:10.1038/srep21010 REFERENCE PMID:15607932 AUTHORS Safaei R, Howell SB TITLE Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. JOURNAL Crit Rev Oncol Hematol 53:13-23 (2005) DOI:10.1016/j.critrevonc.2004.09.007 REL_PATHWAY ko03420 Nucleotide excision repair ko03430 Mismatch repair ko04012 ErbB signaling pathway ko04110 Cell cycle ko04115 p53 signaling pathway ko04210 Apoptosis ///