Researchers discover a link between the tumor microenvironment and fatality rates.
Researchers at the Nagourney Cancer Institute and Metabolomycs recently reported at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans ovarian cancer survival rates can be predicted by using metabolic signatures in a tumor microenvironment. By doing so, oncologists could be able to predict how a patient might fare after being diagnosed and, thus, improve cancer survival rates.
Dr. Robert Nagourney, a leading oncologist and researcher in Los Angeles said, “As we showed in our clinical study published in the October issue of Gynecologic Oncology (D’Amora P. et al October 2021), altered metabolic re-programming measured in the patient’s plasma predicts response and progression of disease in gynecologic cancers. We have now shown that similar results are found in the tumor microenvironment. These findings measured within days of surgery and before any treatment is administered could identify patients at risk for drug resistance or early relapse thereby allowing physicians to change management and improve outcomes.”
Ovarian cancer is currently the leading cause of gynecologic cancer fatalities. The American Cancer Society, SEER data and numerous publications predict that while “80% of ovarian cases respond to platinum-based therapy, the majority of cases recur, leading to death within five years.”
“There is a growing recognition that cancer is not an abnormal cell but an abnormal microenvironment,” explained Nagourney. “Cancers interact with one another, their stroma, their vasculature and inflammatory cells to create a new cellular ecology. This study captured each patient’s ovarian cancer cells in their own unique niche to measure how these cancer cells used nutrients to make energy and create cellular macromolecules like phospholipids that form the cell membrane.”
The team conducted quantitative tandem Mass Spectrometry (MS/MS) on the tissue culture media of human ovarian cancer explants to examine metabolic signatures of the tumor microenvironment following three days of culture in modified RPMI 1640. They found that global metabolic reprogramming can aid in determining a continuum from normality to malignant transformation to drug resistance when it comes to the progression of ovarian cancer.
Nagourney said, “Mass Spectrometry is a technical platform with numerous industrial and medical applications. It allows us to measure minute quantities of chemical species. In the past these were identified as ‘peaks’ that could be compared with established libraries to confirm the presence of a given substance of interest like acetaminophen, opioids or gunpowder. With the advent of targeted mass spectrometry, internal standards placed into each well allow the quantification of the exact amounts of each chemical. Using this approach to measure metabolites in the blood or tissue has offered an entirely new level of sensitivity and specificity that is revolutionizing our understanding of human metabolism in health and disease.”
He explained further, “Life as we know it is based upon the purposeful use of energy. Energy is generated through the process of cellular metabolism. Metabolic disorders result from altered cellular energy production and/or the accumulation of toxic metabolites. Minor deficiencies are present in virtually all individuals but while many of these deficiencies do not result in serious disease, for others, subtle errors of metabolism tip our physiology from normality to disease states like type II diabetes, hypertension and cardiovascular disease all the way to dementia and cancer. Cells incapable of responding to the microenvironmental stresses that are associated with nutrient deficiencies or hormonal imbalances descend into an altered state ultimately culminating in degenerative diseases or neoplasia.”
The Nagourney Cancer Institute is a clinical research center that has been a pioneer in the study of human tumor tissue for individualized cancer patient drug selection and has facilitated cancer drug discovery. Metabolomycs, Inc is a California-based corporation that applies metabolic signatures measured by mass spectrometry to study human health and disease.