The molecular, the bad, and the ugly: preventing bladder cancer via mTOR inhibition.
This perspective on Seager et al. (beginning on p. 1008) considers an important advance in the effort to control bladder cancer. Frontline therapy for superficial transitional cell carcinoma of the bladder involves instillation of the crude immunomodulatory bacterial extract Bacillus Calmette-Guérin directly into the organ. Seager et al. now show that local administration of a chemical inhibitor of mammalian target of rapamycin strongly suppressed growth in a novel preclinical mouse model that develops carcinoma in situ, a particularly problematic form of transitional cell carcinoma of the bladder. The results not only support the clinical evaluation of mammalian target of rapamycin inhibitors in this setting, they open the door for the evaluation of additional molecular local therapies as well.
McConkey
David J
DJ
Department of Urology, Unit 1373, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. dmcconke@mdanderson.org
Dinney
Colin P
CP
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000517:prevention & control*
D000903:Antibiotics, Antineoplastic; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus