Growing research suggests various ways weight loss drugs could have an impact in cancer care.
Growing research suggests various ways weight loss drugs could have an impact in cancer care.
Insulin resistance is a condition, common in obesity and type 2 diabetes, where the body’s cells do not respond properly to insulin, a hormone that controls blood sugar. This review explains how this metabolic problem is a significant risk factor for several major cancers, including those of the breast, liver, and endometrium. The high levels of insulin, chronic inflammation, and altered cellular energy usage associated with insulin resistance create an environment that can fuel the growth and spread of tumors. Since insulin resistance is a modifiable condition, understanding this link opens up new strategies for cancer prevention and treatment, emphasizing the importance of lifestyle interventions and metabolic health.
From WebMD:
Cancer deaths are dropping overall, but not the ones linked to obesity.
That’s what mounting evidence now shows. A sweeping new report on U.S. cancer trends, published in April, revealed that cancers linked to obesity are becoming more common. Another study, presented in July at the Endocrine Society Annual Meeting in San Francisco, found that deaths from obesity-related cancers have more than tripled over the past two decades.
SAN FRANCISCO—Cancer deaths linked to obesity have tripled in the United States over the past two decades, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif.
The study, which examined more than 33,000 deaths from obesity-associated cancers, revealed sharp increases in cancer deaths, especially among women, older adults, Native Americans and Black Americans.
SynDevRx, Inc. today announced the opening of a first-of-its-kind Phase 1b/2 study for patients with triple-negative breast cancer and baseline insulin resistance, testing the novel drug evexomostat (SDX-7320) in combination with standard-of-care treatment Halaven (eribulin, Esai). Evexomostat is among the first anti-cancer therapeutics being developed specifically for cancer patients with baseline metabolic dysfunction (obesity, type 2 diabetes and pre-diabetes). The clinical research study is being conducted in collaboration with New York’s Memorial Sloan Kettering Cancer Center (MSK).
– First prospective study of its kind aims to demonstrate that restoring insulin sensitivity in breast cancer patients with baseline insulin resistance will improve clinical outcomes
– Supports lead investigator Dr. Neil Iyengar of Memorial Sloan Kettering, NY long-term research into the profound and negative influence of metabolic dysfunction (obesity, diabetes, insulin resistance) on breast cancer progression, spread and clinical outcomes
QUT SDX Collaboration Press Release 07Dec 2021
– Part of an ongoing investigation focused on how obesity and dysregulated metabolic hormones promote prostate cancer progression and metastasis
– Studies aim to quantify the ability of SynDevRx MetAP2 inhibitor evexomostat (SDX-7320) to control tumor growth of castration resistant prostate cancers
SynDevRx, Inc., a clinical-stage biotechnology company leading the development of treatments for obesity-accelerated cancers, today announced a research collaboration with Maine Medical Center Research Institute’s Michaela Reagan, PhD. The collaboration will study the role of MetAP2 in obesity-accelerated growth and metastatic potential of multiple myeloma – a form of cancer that develops in bone marrow.
Obesity and systemic metabolic dysfunction are known to make many solid tumors more aggressive, but the connection goes beyond that: multiple myeloma (MM) and several other cancers are also accelerated by systemic issues brought on by obesity, pre-diabetes and type 2 diabetes. MetAP2 inhibitors, such as SDX-7320, have been shown to improve systemic metabolic hormone dysregulation and they demonstrate anti-tumor and anti-angiogenic properties. It’s this combination of attributes that targets the link between obesity and cancer which may prove well-suited to treat MM in combination with standard-of-care therapies.
Obesity and type 2 diabetes have both been associated with increased cancer risk and are becoming increasingly prevalent. Metabolic abnormalities such as insulin resistance and dyslipidemia are associated with both obesity and type 2 diabetes and have been implicated in the obesity-cancer relationship. Multiple mechanisms have been proposed to link obesity and diabetes with cancer progression, including an increase in insulin/IGF-1signaling, lipid and glucose uptake and metabolism, alterations in the profile of cytokines, chemokines, and adipokines, as well as changes in the adipose tissue directly adjacent to the cancer sites. This review aims to summarize and provide an update on the epidemiological and mechanistic evidence linking obesity and type 2 diabetes with cancer, focusing on the roles of insulin, lipids, and adipose tissue.
CDK 4/6 inhibitors are an important drug class in 1st line metastatic breast cancer. Unfortunately, resistance inevitably develops and causes treatment failure and the patient’s cancer progresses. Here we show that SDX-7320 overcomes many of the known mechanisms of developed resistance to CDK 4/6 inhibition. 2021 AACR Poster Apr 2021
Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence.
The opportunity to draw upon genetic data from large-scale, international consortia allows for triangulation of evidence using distinct methodological approaches that make orthogonal underlying assumptions and suffer from distinct sources of bias. The findings of our study
support a potential causal effect of genetically predicted T2DM and/or fasting insulin levels, rather than genetically predicted fasting glucose levels, on risk of breast, endometrial, pancreatic and kidney cancer. These findings are consistent with experimental and molecular epidemiological data which support a role for insulin signalling in the development of several cancers and may therefore represent an important pathway linking T2DM and cancer.
“We would expect at some point cancer would overtake vascular disease as a leading cause of death, both in the general population and among people with diabetes,” Song told Healio. “What surprises me most is the magnitude of the gap. If you look at the number for total cancer deaths, it is almost twice as high as vascular disease. That magnitude highlights the urgency of this issue.”
Jim Shanahan from SynDevRx explains why metabo-oncology treatment modalities could be the answer to a rise in metabolic disorders and cancers.
With a global epidemic of obesity and diabetes and their known relationship to cancer, researchers and oncologists are turning their attention to metabolic hormones as promising new targets for cancer treatment.
Patients that are not cured with surgery or radiation are largely treated with endocrine therapies that target androgens or the androgen receptor (AR), a major driver of PCa. In response to androgen deprivation, most PCas progress to castrate resistant PCa. Epidemiological studies suggest that high-fat diets play important roles in PCa progression. Lipid metabolism rewires the PCa metabolome to support growth and resistance to endocrine therapies, although the exact mechanisms remain obscure. Therapeutic effects have been observed inhibiting several aspects of PCa lipid metabolism, including; synthesis, uptake, and oxidation. Since AR remains a driver of PCa in advanced disease, strategies targeting both lipid metabolism and AR are starting to emerge, providing new opportunities to re-sensitize tumors to endocrine therapies with lipid metabolic approaches.
Obesity has been linked to increased risk for over a dozen different types of cancer, as well as worse prognosis and survival. Over the years, scientists have identified obesity-related processes that drive tumor growth, such as metabolic changes and chronic inflammation, but a detailed understanding of the interplay between obesity and cancer has remained elusive.
In a new study in mice, Harvard Medical School researchers have uncovered a new piece of this puzzle, with surprising implications for cancer immunotherapy: Obesity allows cancer cells to outcompete tumor-killing immune cells in a battle for fuel.
Endogenous hyperinsulinemia has been proposed as one of the causal factors contributing to the association between obesity, diabetes, and increased cancer risk and mortality. Previous studies have examined the mechanisms through which hyperinsulinemia promotes cancer progression, but it is not understood how hyperinsulinemia contributes to cancer incidence. Disruption of cell polarity is an early event in epithelial cancers, and cells that lose polarity are usually eliminated through tumor-suppressive cell competition. Sanaki and colleagues used Drosophila with scrib (scribble planar cell polarity protein) mutant cell clones in the eye disc to understand the mechanisms underlying tumor-suppressive cell competition. They discovered that hyperinsulinemia gives epithelial cancer cells a competitive advantage.
While diabetes/insulin-resistance and breast cancer are distinct diseases, insulin-signaling plays a central role in both illnesses. Insulin activates key cancer processes including EMT, tissue inflammation, motility, and angiogenesis. There are key opportunities to impact and prevent hyperinsulinemia during breast cancer prevention, surgical assessment, and chemotherapy. While it is not standard of care to test for insulin-resistance during the course of breast cancer screening and treatment, it is standard of care to screen and test high risk women for insulin-resistance as part of whole woman care.
We show that decellularized ECM from tumor-bearing and obese mammary glands drives
TNBC cell invasion. Proteomics of the ECM from the obese mammary gland led us to identify full-length collagen
VI as a novel driver of TNBC cell invasion whose abundance in tumor stroma increases with body mass index in
human TNBC patients. Last, we describe the mechanism by which collagen VI contributes to TNBC cell invasion via
NG2-EGFR cross-talk and MAPK signaling.