All our body's natural rhythms of light and dark are synchronized by our biological or circadian clock. Disrupting this clock might simply bring all the process to halt. This may even lead to prostate cancer - second leading cause of cancer death for men in the U.S.
One of the clock genes CRY-1 is found to be involved in prostate cancer progression, as per the research at the Sidney Kimmel Cancer - Jefferson Health (SKCC) published in the journal Nature Communications.
"When we analyzed human cancer data, the circadian factor CRY-1 was found to increase in late stage prostate cancers, and is strongly associated with poor outcomes. However, the role of CRY-1 in human cancers has not been explored", says Karen Knudsen, MBA PhD, executive vice president of oncology services for Jefferson Health and enterprise director of SKCC, and senior author of the study.
CRY1 in Prostate Cancer
The study found that the clock gene CRY-1 is induced by the androgen receptor in prostate tumor tissue obtained from patients. This explains in part the reason for high levels of CRY-1 gene observed in human disease.
Generally cancer therapy involves damaging the DNA in cancer cells and cause defects in their repair mechanisms that ultimately lead to self-destruction of the cancer cells.
The team probed the clock gene in cultured cells, animal models and tissue harvested from prostate cancer patients. When these cancer cells were exposed to radiation that damages its DNA, elevated levels of CRY-1 were observed.
This showed that CRY-1 directly regulates the way that cancer cells repair their DNA, thereby offering a protective effect against damaging therapies. This elevated level of CRY-1 in late-stage prostate cancer demonstrates the ineffectiveness of androgen-targeting treatments at those stages.
"It's been shown that circadian disruptions can affect efficacy of treatment, but also that aligning treatment with the body's natural rhythms or giving therapy at certain times of the day can be beneficial. Our findings open up a multitude of important research questions exploring the link between the circadian clock and cancer", says Dr. Knudsen.
The study emphasizes the pro-tumor role of CRY-1 in prostate cancer and hence plans to explore how best to target and block CRY-1 and what other existing therapies may work synergistically to hinder DNA repair in prostate cancer cells.