How a gene linked to the circadian clock could point to new prostate cancer treatments

Studies have shown that disruptions in circadian rhythms caused by chronic sleep deprivation and other lifestyle-related issues are linked to an increased incidence of some cancers, including prostate cancer.

Researchers at Sidney Kimmel Cancer - Jefferson Health (SKCC) analyzed that connection and landed on a circadian clock gene that seems to play a major role in prostate cancer progression. They believe their findings could inspire new treatments that target the gene, which is called CRY1, they reported in the journal Nature Communications.

The researchers analyzed prostate tissue and found that the CRY1 protein is elevated in late-stage prostate cancer. They discovered that the receptor for the male hormone androgen—a major culprit in the development and progression of prostate cancer—induces CRY1.

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CRY1 is well known for its role in regulating circadian rhythms. Abnormalities in the gene have been tied to sleep-related illnesses like delayed sleep phase disorder, but its role in cancer progression is not well understood.

So the SKCC team probed further, with the aim of determining what role CRY1 might play in DNA repair, because the ability of cancer cells to repair DNA breaks is crucial to their survival. Using the prostate cancer samples, as well as cultured cells and animal models, they induced DNA damage and then tracked levels of CRY1.

Sure enough, CRY1 was elevated in response to DNA damage, suggesting the gene may shield prostate tumors from DNA-damaging treatments.

"The fact that CRY1 is elevated in late-stage prostate cancer may explain why androgen-targeting treatments become ineffective at those later stages," said lead author Ayesha Shafi, Ph.D., a postdoctoral researcher at Jefferson Health, in a statement. "It also tells us that if a tumor has high levels of CRY1, DNA repair targeting treatments may be less effective for them."

Other research teams are examining the role of clock genes in cancer progression. Last year, a City of Hope team described a link between the clock gene BMAL1 and breast tumor growth in mouse models of obesity and prediabetes. In that case, a deficiency in the BMAL1 protein that can occur with obesity promoted the growth and spread of breast tumors. The researchers continue to study the association between BMAL1 and cancer in prediabetic, obese patients.

The next step for the SKCC team is to explore therapies that can target and block CRY1, including currently marketed cancer drugs, they said. They also plan to study other genes that are involved in circadian rhythm to better understand the role that clock genes play in cancer treatment.