Bisphenol A may reduce the efficacy of androgen deprivation therapy in prostate cancer.
Individuals diagnosed with specific diseases may represent subpopulations with heightened sensitivity to environmental compounds. This may be due to their disease-mediated molecular milieu and/or the interference of environmental compounds with pharmaceutical drug targets. Prostate cancer represents a significant clinical challenge in the United States. If the disease becomes advanced, standard therapies are ineffective, leading to high rate of patient morbidity and mortality. Understanding the complex reasons for therapeutic resistance is critical for improving the life expectancy for patients with this cancer. Recently, it has been identified that common somatically derived genetic mutations that arise following the selective pressure of standard prostate cancer treatments may facilitate sensitivity to environmental contaminants. These somatic mutations within the androgen receptor allow the estrogen mimic, bisphenol A (BPA), to bind and activate the receptor, resulting in increased proliferation and tumor growth in the presence of the traditional therapy regimen for prostate cancer. In an in vivo xenograft model of prostate cancer, low level exposure of BPA was sufficient to reduce the efficacy of treatment. Herein, the possible effect of BPA on prostate cancer treatment and disease management for humans is explored as an example of environmental endocrine disruptor exposure reducing the efficacy of disease management. These data lend support to the hypothesis that environmental exposure to select compounds may interfere with specific therapeutic regimens.
Janet K
JK
Hess-Wilson
D000230:Adenocarcinoma / Q000628:therapy*; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000502:physiology; D001559:Benzhydryl Compounds; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D006801:Humans; D008297:Male; D010636:Phenols / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000628:therapy*; D011944:Receptors, Androgen / Q000378:metabolism; D016896:Treatment Outcome; D000098826:Bisphenol A Compounds
D059002:Androgen Receptor Antagonists; D000728:Androgens; D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011944:Receptors, Androgen; C006780:bisphenol A; D000098826:Bisphenol A Compounds