Circadian Cancer Therapy

William Hrushesky, MD FACP, Founder and Chief Scientific Officer Rythmalytics LLC (Cicada Circadian Coach), West Orange NJ; Chief Medical Officer Ambulatory Monitoring Inc., Ardsley, NY

Q: Are there meaningful advantages to show for optimizing and specifying time of day treatments for cancer?
A: Everyone knows: GEICO can save you 15%. Everyone knows “Timing is everything”. Almost no one knows: the time of day cancer therapy is given determines the severity of its toxicities, its anti-cancer efficacy and the likelihood of five year advanced cancer patient survival (four fold).
Some 25 years ago, a physicist and engineer, since friend and research collaborator, read of our circadian cancer therapy work in “Science” and came to visit me.
He had just had a colon cancer resected. This cancer was very mean and aggressive under the microscope and involved many lymph nodes. He had been told that he should undergo multi-agent chemotherapy. He was also told his cancer would probably recur and kill him within a few months or years, despite this highly toxic chemotherapy. Mike is a compulsive bike rider & athlete and had read about our work, creating, programmable continuous infusion pump based regimens with little or no toxicity and greater efficacy in metastatic colorectal cancer when given by continuous infusion, mostly at the right time of each day. I told him that such data were solid but that we had not done post surgical adjuvant (after surgery to increase cure) studies.
He and I created an adjuvant regimen which provided the vast majority of each day’s continuous 24 hour infusion in the night time hours, when in the day our clinical studies demonstrated unequivocally the patient would be spared the most damaging ill effects. Within six months this 24 hour continuous personalized timed chemotherapy regimen devolved into a night time only regimen with weekend breaks. We repeatedly found no evidence for cancer recurrence. Mike had NO side effects and continued to ride his bike 50 miles each day. After close to two years of this completely benign timed infusional therapy, I asked Mike whether he wished to stop. He did. That was more than two decades ago.
Mike now studies the metastatic process and interrupting it. We have written some thirty papers together, have earned two grants to support this work and are working on a third.
The five billion years of life on this planet, characterized by the continuous rhythmic dynamic dance of earth and sun have endowed each earthborn life form with hierarchies of circadian clocks. Molecular clocks inhabit and beat within each cell. A range of neurologic (SCN and retinal) and neuro-endocrine (pineal) physiologic clocks, time each and every life event optimally within each day. The blue wavelength (dawn & dusk) sensitive retinal ganglia clocks connect the brain, pineal and cellular clocks directly to the sun each and every day. Cancer cells maintain this coordinated daily biology.
Nearly every useful anti-cancer agent targets aspects of highly coordinated circadian organized cellular proliferation. Human beings living in a single time zone share time of day, intimately, providing potential temporal personalized synchrony.
In cancer therapy timing is “everything”. Forty years of work and thousands of peer reviewed publications back this up and await immediate application.
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