This Study Reveals Why Timing Your Cancer Treatment Could Be the Key to Survival

Why the timing of your treatment might determine whether you beat cancer or not.

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My Longevity Experiment
August 19, 2024

This Study Reveals Why Timing Your Cancer Treatment Could Be the Key to Survival

Cancer Treatment

Why the timing of your treatment might determine whether you beat cancer or not.

A study conducted by the Sidney Kimmel Cancer Center has revealed a significant connection between a circadian rhythm gene and the effectiveness of cancer treatments, emphasizing the potential impact of treatment timing on therapeutic outcomes.

The circadian clock, which aligns the body's processes with the natural cycles of light and dark, plays a critical role in maintaining health. Disruptions to this biological clock, such as those caused by sleep deprivation, jet lag, or shift work, have been linked to an increased risk of various cancers, including prostate cancer—the second leading cause of cancer death among men in the United States.

Given these findings, there is an urgent need to identify new therapeutic targets for prostate cancer. Researchers at the Sidney Kimmel Cancer Center have focused on the circadian clock, discovering an unexpected role for the clock gene CRY-1 in the progression of cancer.

Karen Knudsen, MBA, Ph.D., Executive Vice President of Oncology Services for Jefferson Health and Enterprise Director of SKCC, and senior author of the study, stated, "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 CRY-1 [plays] in human cancers has not been explored."

Prostate cancer therapy commonly involves suppressing the male hormone androgen and/or its receptor, as androgens are crucial for the development and progression of prostate tumors. The research team, in collaboration with experts from the U.S. and Europe, found that CRY-1 is induced by the androgen receptor in prostate tumor tissue obtained from patients. This discovery partially explains the elevated levels of CRY-1 observed in human prostate cancer.

Ayesha Shafi, Ph.D., a post-doctoral researcher in the Knudsen Lab and the study's first author, commented, “This was a clear indication of CRY-1's link to prostate cancer. As we looked further into the role of CRY-1, we unexpectedly found that the circadian factor was altering the way that cancer cells repair DNA."

Cancer treatments typically aim to damage the DNA in cancer cells, causing defects in repair mechanisms that ultimately lead to cell death when the damage is extensive. The researchers investigated CRY-1's potential role in DNA repair using cultured cells, animal models, and tissue samples from prostate cancer patients.

Their initial findings revealed that exposing cancer cells to radiation, which induces DNA damage, led to elevated levels of CRY-1, suggesting a response to the damage. Moreover, CRY-1 was found to directly regulate the availability of factors essential for DNA repair and alter the way cancer cells respond to DNA damage. These findings indicate that CRY-1 may provide a protective effect against therapies designed to damage DNA.

Dr. Shafi stated, "The fact that CRY-1 is elevated in late-stage prostate cancer may explain why androgen-targeting treatments become ineffective at those later stages. It also tells us that if a tumor has high levels of CRY-1, DNA repair targeting treatments may be less effective for them."

Dr. Shafi further emphasized, "Not only have we outlined a role for CRY-1 outside of its canonical function in circadian rhythms, but our findings are the first to reveal the means by which CRY-1 contributes to aggressive disease. It's notable that the pro-tumor functions of CRY-1 may be viable targets to treat prostate cancer, and this is a direction that our future work will explore."

Looking forward, the research team plans to investigate strategies to target and block CRY-1, as well as explore other existing therapies that may work synergistically to impair DNA repair in prostate cancer cells. Dr. Knudsen concluded, "It's been shown that circadian disruptions can affect the efficacy of treatment, but also that aligning treatment with the body's natural rhythms or administering 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."

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