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Ozempic for cancer? Signs point to potential benefits of GLP-1s in oncology.
Growing research suggests various ways weight loss drugs could have an impact in cancer care.
The Role of Insulin Resistance in Cancer
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.
Obesity-Cancer Link: It’s Worse Than You Think
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.
Obesity-associated cancers tripled nationwide over 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.
Evexomostat Phase 1 Clinical Safety Study in Late-Stage Cancer Patients
$1.2M Grant Awarded for Groundbreaking Prostate Cancer Research on SynDevRx MetAP2 Inhibitor ‘Evexomostat’
Cambridge, MA (USA) and Brisbane (Australia) – Queensland University of Technology (QUT) in Brisbane, Australia, together with SynDevRx, Inc., a leader in polymer-drug conjugates for cancer and for metabolic dysfunction are honored to announce the receipt of a $1.2 million grant from the US Department of Defense (DoD) for continued research on evexomostat, SynDevRx’s novel clinical drug candidate targeting late-stage, androgen receptor pathway inhibitor resistant prostate cancer. More specifically, the research grant will fund both a pilot clinical study and mechanistic research in the lethal form of late-stage prostate cancer referred to as ‘Aggressive Variant’ (AVPC), including the challenging neuroendocrine tumor phenotype. This award was based on evexomostat’s surprisingly potent pre-clinical activity in PDX prostate cancer models.EINPresswire-775270180-1-2m-grant-awarded-for-groundbreaking-prostate-cancer-research-on-syndevrx-metap2-inhibitor-evexomostat 08Jan 2025
AACR Journal MCT Publishes Initial Disclosure Article on Evexomostat/SDX-7320
Pharmacological Characterization of SDX-7320/Evexomostat: a Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-Tumor and Anti-Metastatic Activity
Methionine aminopeptidase type 2 (MetAP2) is a ubiquitous, evolutionarily conserved metalloprotease fundamental to protein biosynthesis which catalyzes removal of the N-terminal methionine residue from nascent polypeptides. MetAP2 is an attractive target for cancer therapeutics based upon its over-expression in multiple human cancers, the importance of MetAP2-specific substrates whose biological activity may be altered following MetAP2 inhibition, and additionally, that MetAP2 was identified as the target for the anti-angiogenic natural product, fumagillin. Irreversible inhibition of MetAP2 using fumagillin analogs has established the anti-angiogenic and anti-tumor characteristics of these derivatives, however, their full clinical potential has not been realized due to a combination of poor drug-like properties and dose-limiting CNS toxicity. This report describes the physicochemical and pharmacological characterization of SDX-7320 (evexomostat), a polymer-drug conjugate of the novel MetAP2 inhibitor (MetAP2i) SDX-7539.
Amelia-1 Clinical Trial Fully Open To Recruitment, 1st Patient Data on Combination Study with PI3K Inhibitor and SERD
SynDevRx, Inc. today announced the opening of the Amelia-1 study and data from the first patient treated in its Phase 1b/2 clinical study testing the novel MetAP2 inhibitor evexomostat (aka SDX-7320) in combination with the PI3K inhibitor alpelisib (Piqray®) and the estrogen receptor degrader (SERD) drug fulvestrant (Faslodex®) in breast cancer patients with metastatic disease and the PIK3CA gene mutation (NCT05455619 – Phase 1b/2 Study of the Safety and Efficacy of Evexomostat Plus Alpelisib and Fulvestrant in Postmenopausal Women at Risk for Hyperglycemia With Advanced Breast Cancer and a PIK3CA Mutation Following Endocrine Therapy and a CDK4/6 Inhibitor).
Amelia™-1 Study is testing if evexomostat can improve patients’ safety and clinical response to a PI3K inhibitor plus an estrogen receptor degrader. Evexomostat, a novel MetAP2 inhibitor, controlled PI3K-induced hyperglycemia in the first study patient, consistent with pre-clinical data. Further, ctDNA data shows no evidence of residual PIK3CA mutation in blood after 6 weeks of treatment.
New Experimental Treatment for Prostate Cancer Revealed at AACR
SDX AACR 2023 poster 05Apr 2023.pptx
PRESS RELEASE • APR 14, 2023 08:00 EDT
Evexomostat (SDX-7320) shows potent anti-tumor effects in pre-clinical models of prostate cancer, including castration-resistant. New research data to be presented at AACR 2023 in Orlando, FL
SynDevRx Joins ‘Touch – The Black Breast Cancer Alliance’ CEO Ricki Fairley in Metabo-Oncology Podcast – Wed. Oct 5, 2022 at 6:00 PM
Aug. 31, 2022 – SynDevRx Presents Scientific Poster on Anti-Fibrosis Data with Evexomostat at the 2022 IPF Conference in Boston
Aug. 31, 2022 – SynDevRx, Inc., a clinical-stage biotechnology company leading the development of treatments for obesity-accelerated cancers, today announced the presentation of new scientific data on its lead compound evexomostat (SDX-7320) in a series of fibrosis models demonstrating potent anti-fibrosis data monotherapy and in combination with the standard of care therapy nintedanib. Evexomostat significantly improved lung function following lung injury, reduced fibrotic foci, and reduced lung edema both alone and even more potently when combined with nintedanib. Poster Presentation: 2022 IPF Summit
Breast Cancer Conversations: What You Need To Know About Your Metabolic Health and Breast Cancer
What You Need To Know About Your Metabolic Health and Breast Cancer
Breast Cancer Conversations is a podcast that discusses all things breast cancer! We share stories of those who have been diagnosed. We interview medical professionals, doctors, radiologists, and oncologists. We speak with advocates and caregivers. We are your voice! If you have questions, we go out and seek answers! We break it down to understandable terms and build community for our thriving tribe.
Welcome to the conversation.
New Phase 1b/2 Clinical Research Study with SynDevRx Drug Evexomostat (SDX-7320) Announced for Triple-Negative Breast Cancer Patients with Baseline Insulin Resistance
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
Prostate Cancer Research Collaboration with Australia Univ. of Technology, Prof. Colleen Nelson, PhD
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
2021 San Antonio Breast Cancer Symposium Poster Presentation (SDX-7320+Capivasertib in Her2+ model)
SynDevRx Announces Research Collaboration with Maine Medical Center Research Institute to Study the Effects of SDX-7320 In Obesity-Accelerated Multiple Myeloma Models
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, Type 2 Diabetes,and Cancer Risk
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.
SDX Presents New Oncology Data at 2021 AACR Showing Reversal of Resistance Mechanisms to CDK4/6 Inhibitors
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
Effects of Diet and Exercise induced Weight Loss on Biomarkers of Inflammation in Breast Cancer Survivors
Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence.
Type 2 diabetes and cancer: an umbrella review of observational and Mendelian randomisation studies
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.
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