By National University of Singapore, Yong Loo Lin School of Medicine June 12, 2024
A groundbreaking cancer treatment developed by NUS researchers utilizes engineered bacteria to deliver chemotherapy drugs directly to tumor sites, significantly enhancing treatment efficacy and reducing side effects.
Researchers at NUS Medicine have engineered bacteria to deliver chemotherapy in a targeted manner.
Traditional chemotherapy frequently presents substantial difficulties, such as harsh side effects, harm to healthy cells, and restricted effectiveness.
Researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have pioneered a groundbreaking cancer treatment method. This new technique offers a more precise, potent, and less harmful alternative to conventional chemotherapy. It not only enhances the efficacy of the treatment but also substantially lowers the dosage of drugs needed for cancer therapy.
Led by Associate Professor Matthew Chang, researchers at the NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) and the Synthetic Biology Translational Programme (Syn Bio TRP) at NUS Medicine identified a new method of drug delivery that offers hope for the development of a new clinical treatment for cancer patients. The findings, published in Nature Communications, showcase a novel method for delivering chemotherapy drugs directly to tumor sites by utilizing the natural interactions between bacteria and cancer cells.
Prodrug Strategy and Bacterial Innovation
Prodrugs are inactive molecules that transform into active drugs within the body, particularly in tumor environments, by leveraging unique tumor conditions, such as low oxygen or high acidity, to activate the drug precisely at the cancer site, minimizing damage to healthy tissues. However, current prodrug strategies exhibit limited target specificity and frequently depend on macromolecular carriers, which complicates both drug distribution and clearance.
To overcome these limitations, NUS Medicine researchers developed a prodrug delivery method that utilizes a commensal Lactobacillus strain that binds specifically to cancer cells via a surface molecule called heparan sulfate. These engineered bacteria carry a prodrug that converts to the chemotherapy drug SN-38 at the tumor site. In preclinical models of nasopharyngeal cancer, the engineered bacteria localized specifically in the tumor and released the chemotherapy drug directly at the cancer site, reducing tumor growth by 67% and increasing the effectiveness of the chemotherapy drug by 54%.
Potential for Wider Cancer Treatment Applications
One of the most promising aspects of this research is the potential broader applications across various types of cancer therapy, as the Lactobacillus strain identified by the researchers binds specifically to cancer cells. Lead Researcher Dr Shen Haosheng, Research Fellow at SynCTI said: “By harnessing the affinity between bacteria and cancer cells, we aim to revolutionise chemotherapy delivery. We are evaluating the binding affinity of several microbial strains to multiple cancer cell lines with the aim of developing a versatile delivery system using microbial strains to target chemotherapy drugs to various mucosal cancers, such as colorectal, bladder, stomach, oral, lung, and nasal cancer.”
“Cancer treatment often takes a tremendously heavy toll on patients. Our research represents a significant step toward developing a more targeted and less toxic approach to fighting cancer. We hope this can pave the way for therapies that are both mild and effective,” added A/Prof Chang, Dean’s Chair in Medicine and Director of SynCTI and NUS Medicine Syn Bio TRP.
Reference: “Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy” by Haosheng Shen, Changyu Zhang, Shengjie Li, Yuanmei Liang, Li Ting Lee, Nikhil Aggarwal, Kwok Soon Wun, Jing Liu, Saravanan Prabhu Nadarajan, Cheng Weng, Hua Ling, Joshua K. Tay, De Yun Wang, Shao Q. Yao, In Young Hwang, Yung Seng Lee and Matthew Wook Chang, 21 May 2024, Nature Communications.
DOI: 10.1038/s41467-024-48661-y
Research from Geisinger Medical Center shows Roux-en-Y gastric bypass surgery holds type 2 diabetes in remission for 15 years and supports sustainable weight loss for 20 years, underscoring its long-term effectiveness over other treatments.
Gastric bypass keeps diabetes in remission for 15 years and weight loss maintained for 20 years, according to a large, long-term study.
Roux-en-Y gastric bypass, a type of weight-loss surgery, kept type 2 diabetes in remission for up to 15 years and most of the weight off for up to 20 years in one of the largest long-term studies of patients undergoing the procedure. The study “Long Term (> 15 Year) Outcomes Following Roux-en-Y Gastric Bypass” will be presented today (June 12) at the American Society for Metabolic and Bariatric Surgery (ASMBS) 2024 Annual Scientific Meeting.
Study Details and Initial Findings
Researchers from Geisinger Medical Center in Danville, Pennsylvania analyzed diabetes remission rates and weight-loss outcomes of 2,045 patients who had a gastric bypass at their center between 2001 and 2008 and followed them for up to 20 years. Patients, on average, were 46 years old with a body mass index (BMI) of 47.9, prior to surgery.
Of the 677 patients with pre-operative diabetes, remission rates were 54% at the three-year mark but dropped to 38% after 15 years. Only about 10% of patients with insulin-dependent diabetes had remission in the same timeframe and the rate of persistent diabetes was higher in patients who had insulin-treated diabetes before surgery.
About Weight-Loss SurgeryMetabolic, bariatric, or weight-loss surgery such as gastric bypass and sleeve gastrectomy has been shown to be the most effective and long-lasting treatment for severe obesity. The operations improve or resolve diseases including type 2 diabetes, heart disease and high blood pressure and leads to significant and durable weight loss. Its safety profile is comparable to some of the safest and most commonly performed surgeries in the U.S. including gallbladder surgery, appendectomy, and knee replacement.
Surgical Safety and Mortality Rates
Peak weight loss of 31.8% was achieved after 18 months and stabilized at 23% after 10 years and up to the 20-year mark. The overall 15-year mortality rate was 13.3%, which was 37.4% among patients with diabetes and older than 60. No deaths were related to the surgical procedure itself.
“With the availability of medical and endoscopic therapies, the demonstration of long-term effectiveness of gastric bypass that exceeds that of these alternatives is critical to providing the right intervention for the right patient at the right time,” said study author Anthony T. Petrick, MD, FACS, Director, Division of Bariatric and Foregut Surgery, Geisinger Health System.
Prevalence and Eligibility for Bariatric Procedures
The ASMBS reports that nearly 280,000 metabolic and bariatric procedures were performed in 2022, which represents only about 1% of those who meet eligibility requirements based on BMI.
“The study is an important contribution to the current understanding of long-term outcomes of gastric bypass because of the extremely high follow-up rates,” said Marina Kurian, MD, ASMBS President, who was not involved in the study.
According to the U.S. Centers for Disease Control and Prevention (CDC), obesity effects 42.4% of Americans. Studies show the disease can weaken or impair the body’s immune system and cause chronic inflammation and increase the risk of many other diseases and conditions including cardiovascular disease, stroke, type 2 diabetes, and certain cancers.
A447 — Long Term (> 15 Year) Outcomes Following Roux-en-Y Gastric Bypass
John Nguyen-Lee Danville PA, Michael Furey Dallas PA, Craig Wood Danville PA, Luis Pina Danville PA, Mark Mahan Danville PA1, Ryan Horsley Scranton PA, Benefsha Mohammad Danville PA, Alexandra Falvo Scranton PA, Christopher Still Danville PA, Peter Benotti Danville NY, David Parker Danville PA, Vladan Obradovic Manlius NY, Anthony Petrick Danville PA, Geisinger Medical Center
