Molecular mechanisms of cisplatin resistance in bladder cancer.
Metastatic disease is the most common mechanism of death in patients with advanced bladder cancer. As for most solid tumors, chemotherapy remains the only realistic option for palliating or curing metastatic disease. However, bladder cancer is characterized by chemoresistance. Only modest response rates are obtained using multiagent regimens including cisplatin. These low response rates and the toxicity of these regimens limit their use to patients at highest risk. Here, we review the molecular mechanisms of cisplatin resistance. These include methods to reduce cisplatin bioavailability within a cell, and defects in the machinery that produces cell death following cisplatin-induced DNA damage. While overcoming these mechanisms is a potential therapeutic approach that can increase response rates, in the short term this knowledge could be used to predict response in individual tumors.
Institute for Cancer Studies and Academic Urology Unit, University of Sheffield, Sheffield, S10 2RX, UK. r.m.drayton@sheffield.ac.uk
Ross M
RM
Drayton
James W F
JW
Catto
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D002945:Cisplatin