Circadian Clocks and How They Relate to Cancer Treatment

According to Sleep Review, researchers at the University of North Carolina School of Medicine are studying DNA repair after damage from anti-cancer drugs as well as DNA repair and how it relates to one’s circadian clock. This research may have implications for many different types of cancers including testicular and ovarian cancers, as the treatment in the study is a chemotherapy that targets these among others.

What is Ovarian Cancer?

Ovarian cancer is the type of cancer that is found in a female’s ovaries. In ovarian cancer, cancer cells are normally found inside or near the outer layer of the ovaries. The cancer may also spread to the abdomen lining, bowel and bladder lining, lymph nodes, lungs, and liver. There are different types of ovarian cancer as well as BRCA-mutated ovarian cancer, and some symptoms include bloating, pelvic pain, loss of appetite, and urinary symptoms. Treatment options for ovarian cancer depend on the type and stage of the cancer. To read more about ovarian cancer, click here.

What is Testicular Cancer?

Another type of cancer this news may apply to, and is also related to the reproductive system, is testicular cancer. Testicular cancer is cancer in the testes, which functions in the male body for making the hormone testosterone and sperm. There are two main types of testicular cancer called seminomas and non-seminomas, and these vary by onset age. To learn more about the risk factors, symptoms, and treatments for this type of cancer, click here.

Circadian Rhythm and DNA Repair

Aziz Sancar, MD, PhD, from University of North Carolina School of Medicine is analyzing both the body’s circadian clock and DNA repair. More importantly, Sancar is trying to figure out the relation between the two. Though we know the body’s circadian clock rhythm is crucial for our organs to function, Sancar wants to know how this rhythm specifically interacts with basic biology like that of DNA repair.

Sancar and his lab successfully found a way to measure DNA repair after cisplatin, an anti-cancer drug, had damaged the DNA. Sancar’s lab measured DNA repair post-cisplatin treatment throughout a whole 24-hour circadian cycle throughout the genome of a mammal.

From analyzing this data, they were able to find where exactly the genome was being repaired, which individual genes were being repaired, and at what time.

About Cisplatin

The treatment in this study is called cisplatin, and it is a form of intravenous chemotherapy that is used to treat many cancers such as testicular cancer, lung cancer, head and neck cancer, bladder cancer, lymphomas, ovarian cancer, germ cell tumors, and cervical cancer. The treatment works by effectively killing cancer cells by binding to parts of the cancer cell DNA. The drawback to cisplatin, however, is that it is toxic to kidneys, the liver, and the nervous system.

To adjust for these issues with the treatment, scientists are trying to find ways to reduce the toxicity of cisplatin. One method of doing this may be through chronotherapy, which is a type of therapy that delivers treatment in accordance to patients’ biological clocks.

In previous studies, this type of treatment has been attempted, but without the knowledge of DNA repair at the same time. Sancar argues that taking this into account is crucial in analyzing the information.

Co-author of the study, Chris Selby, PhD, elaborates:

“Our approach is to understand the precise mechanistic underpinnings of DNA repair and the circadian clock. With this knowledge, we could tailor chemotherapy treatments accordingly.”

Findings

After studying these two facets of cancer care, the lab found that repair of genes that were involved in transcription peaked at pre-sunrise or pre-sunset, but repair of non-transcribed genes peaked only at pre-sunset.

Understanding when cells in different organs go through DNA repair will help doctors learn the most prime times to administer treatments. Ideally, the best approach would be to deliver treatments when the natural DNA repair process it at its peak.

To learn more about this cancer research, click here.


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