Prof. Jonathan Nyce

Jonathan Nyce

ACGT Biotechnology, USA

Title: The Purpose of Adrenarche is Tumor Suppression

Abstract

Adrenarche is that developmental period during which the adrenal zona reticularis differentiates into a tissue capable of synthesizing and secreting dramatic amounts of dehydroepiandrosterone sulfate (DHEAS) into the bloodstream. It occurs during adolescence just prior to the growth spurts which push the individual forward toward adult body size— which has a greater number of cells at risk of becoming malignant. The purpose of adrenarche remains unknown. The paradigm that has dominated cancer research for the past many decades holds that cancer is the same disease from one species to the next— the notion that was used to justify the use of mouse models to study human cancer. This laboratory has discovered a here-to-fore unrecognized, human-specific “kill switch” tumor suppression mechanism in which circulating DHEAS is imported into cells that have undergone malignant transformation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993206/). Mice have undetectable levels of circulating DHEAS, demonstrating that this species has evolved a totally different mechanism of tumor suppression. In fact, this laboratory has provided evidence that every vertebrate species has evolved its own unique, species-specific “kill switch” mechanism of tumor suppression, with primates apparently the only lineage incorporating DHEAS into theirs. Vertebrate species other than humans (and dogs) have very low lifetime cancer risk (2-5%), risk that remains flat with advancing age. In sharp contrast, human cancer risk has now approached 50%, and such risk increases exponentially as we age. This anomaly can be explained by the fact that the synthesis and secretion of DHEAS reaches a peak at age 25, and dramatically declines thereafter, such decline correlating with the exponential increase in our cancer risk. Because DHEAS is a small molecule, it is pharmacologically tractable. We suggest, therefore, that “normalization” of human cancer risk to the 2-5% of other vertebrate species may be possible by pharmacologically maintaining circulating DHEAS at its peak levels

Biography

Jonathan Nyce completed his Ph.D. at the Fels Cancer Research Institute in 1983, where he presented the first published evidence that tumor DNA is undermethylated compared to normal cells. He subsequently discovered a previously unknown mechanism of drug resistance—drug-induced DNA hypermethylation. He also established that this epigenetic mechanism of drug resistance could be reversed using methylation inhibitors, resulting in re-sensitization of tumors to the drugs that they had become resistant to. He subsequently did postdoctoral research at the Children’s Hospital of Los Angeles, where he and clinical colleagues demonstrated that such epigenetic reversal was also possible in pediatric patients with drug- resistant AML, resulting in complete remissions— the first time that the drug-resistant state had ever been reversed in humans. As a professor in the Department of Pharmacology at the Brody School of Medicine in North Carolina, he extended this work (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46216). In 2015, Professor Nyce discovered that every vertebrate species has evolved a species-specific mechanism of tumor suppression. This discovery challenges the dominant paradigm, which holds that cancer is more or less the same disease from one species to another— the rationale that was used to justify the use of mice to study human cancer