Behavioral stress can accelerate the development of prostate cancer and weaken the effectiveness of drugs designed to fight the disease, researchers have discovered.

Men with prostate cancer have increased levels of stress and anxiety, acknowledged George Kulik, DVM, PhD, associate professor of cancer biology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, and colleagues in The Journal of Clinical Investigation (2013;123[2]:874-886). They also pointed out that men who take beta-blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer.

Kulik’s team tested the effects of behavioral stress in two different mouse models of prostate cancer. In one model, mice were implanted with human prostate cancer cells and given ZSTK474, currently in clinical trial for treatment of the disease. An inhibitor of the P13K pathway, ZSTK474 destroyed prostate cancer cells and inhibited tumor growth when the mice were kept calm and free of stress with a selective beta2 adrenergic receptor antagonist. When the mice were stressed, however, cancer cell death did not occur and ZSTK474 did not inhibit tumor growth.

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The second model involved mice that were genetically modified to develop prostate cancer. The size of their prostate tumors increased when the mice were stressed (exposed to the scent of a predator). The tumors did decrease in size when the mice received bicalutamide, a nonsteroidal antiandrogen, but if the mice were subjected to repeated stress, they exhibited a significantly reduced response to the drug.

Noting that stress did not promote prostate tumor growth in either model in which beta-blockers were used, Kulik commented in a statement issued by his medical center, “Providing beta-blockers to prostate cancer patients who [have] increased [adrenaline] levels could improve the effectiveness of anticancer therapies.”

He added that his group’s findings could be used to identify men with prostate cancer who would benefit from stress reduction or from pharmacologic inhibition of stress-inducing signaling.