Author Interviews, Cancer Research / 17.12.2025
Icahn Mount Sinai Scientists Engineer mRNA to Selectively Target Cancer Cells
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Dr. Zak[/caption]
MedicalResearch.com Interview with:
Magdalena M. Żak, PhD
Zangi Lab
Instructor | Cardiovascular Research Institute
Instructor | Genetics & Genomic Sciences
Icahn School of Medicine at Mount Sinai
Hess Center for Science and Medicine
New York, NY 10029
MedicalResearch.com: What is the background for this study?
Response: mRNA has proven to be a groundbreaking technology through COVID-19 vaccines, and most mRNA-based therapeutics in development today are still focused on vaccines. However, in principle, mRNA could be used for many diseases in which expression of a therapeutic protein would be beneficial. A major reason mRNA is less commonly used outside of vaccines is the lack of robust targeting: for vaccination, broad expression can be acceptable because the goal is antigen production for immune recognition, but for other applications - especially cancer - targeted delivery and minimized off-target expression are critical to reduce side effects. Current targeting strategies largely rely on lipid nanoparticles (LNPs), which act as lipid “carriers” for systemic delivery. Although LNPs can be designed to show some tissue tropism, this is often limited to organs such as the liver, spleen, and lungs.
Dr. Zak[/caption]
MedicalResearch.com Interview with:
Magdalena M. Żak, PhD
Zangi Lab
Instructor | Cardiovascular Research Institute
Instructor | Genetics & Genomic Sciences
Icahn School of Medicine at Mount Sinai
Hess Center for Science and Medicine
New York, NY 10029
MedicalResearch.com: What is the background for this study?
Response: mRNA has proven to be a groundbreaking technology through COVID-19 vaccines, and most mRNA-based therapeutics in development today are still focused on vaccines. However, in principle, mRNA could be used for many diseases in which expression of a therapeutic protein would be beneficial. A major reason mRNA is less commonly used outside of vaccines is the lack of robust targeting: for vaccination, broad expression can be acceptable because the goal is antigen production for immune recognition, but for other applications - especially cancer - targeted delivery and minimized off-target expression are critical to reduce side effects. Current targeting strategies largely rely on lipid nanoparticles (LNPs), which act as lipid “carriers” for systemic delivery. Although LNPs can be designed to show some tissue tropism, this is often limited to organs such as the liver, spleen, and lungs.
Dr. Serena Guo[/caption]
Serena Jingchuan Guo, MD PhD
Assistant Professor
Department of Pharmaceutical Outcomes and Policy
University of Florida College of Pharmacy
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Dr. Hao Dai[/caption]
Hao Dai, PhD
Postdoctoral Fellow
Department of Biostatistics & Health Data Science
Indiana University School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Obesity and type 2 diabetes are both known to increase the risk of several cancers. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become very popular for both glycemic control and weight loss, but their long-term effects on cancer risk are still unclear. Using a large real-world dataset, we emulated a target trial comparing more than 43,000 GLP-1RA users to matched non-users.
We found that GLP-1RA use was associated with a significantly lower overall cancer risk.
Dr. Jiyoung Ahn[/caption]
MedicalResearch.com Interview with:
Jiyoung Ahn, PhD
Dr. Campanella[/caption]
Gabriele Campanella, PhD
Assistant Professor
Windreich Department of Artificial Intelligence and Human Health
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: Lung cancer is the most lethal cancer in the US. Lung adenocarcinoma (LUAD) is the most common form of lung cancer with an incidence of over 100k per year in the US. EGFR mutations are common driver mutations in LUAD, and importantly, these mutations can be targeted by TKI therapy, which has high response rates. Because of this, EGFR testing via NGS (Next Generation Sequencing) is considered mandatory by guidelines for any LUAD diagnosis.
In high-resource settings, rapid EGFR testing is done while waiting for confirmation via NGS. This is because NGS takes about 2 weeks on average, while the rapid testing has a median TAT of 2 days. Early treatment decisions could be made based on the rapid test results. Rapid tests have some important drawbacks, most notably, it exhausts tissue. In lung cancer, tissue is scarce in the first place, and up to 25% of cases, after rapid testing there is not enough tissue for NGS. In those circumstances, patients have to be biopsied again, which adds unnecessary risk for the patient. Even worse, in some cases, the NGS is never done. A non-tissue-exhaustive computational biomarker could be used instead of the tissue-based rapid test.
Dr. Lopes[/caption]
Gilberto Lopes, M.D.
Professor, Chief, Division of Medical Oncology
Associate Director for the Cancer Center and
Medical Director for International Affairs
Sylvester Comprehensive Cancer Center
MedicalResearch.com: What is the background for this study?
Response: There is growing evidence linking alcohol consumption to increased cancer risk and mortality. This association was recently emphasized by the former U.S. Surgeon General, prompting renewed public health interest. In response to these concerns, under the mentorship of Dr. Lopes, we evaluated national trends in alcohol-associated cancer mortality using data from the Global Burden of Disease database.
Dr. Corley[/caption]
Douglas Corley, MD, PhD
Chief Research Officer, The Permanente Medical Group
Kaiser Permanente, Northern California
MedicalResearch.com: What is the background for this study?
Response: Kaiser Permanente Northern California (KPNC) is an integrated health care system that designs and implements population-based programs that support cancer prevention and early detection. In 2006, KPNC began to implement a comprehensive colorectal cancer screening program with the goal of increasing member screening rates, preventing colorectal cancer through polyp removal, and reducing cancer mortality. The initiative identifies whether screening-eligible KPNC members are up to date with their colorectal cancer screening test by either a colonoscopy or by stool-based tests, such as a fecal immunochemical testing (FIT) kit. If they are not up to date with screening, it mails them a FIT kit for at-home testing. Members can also choose other options for colorectal cancer screening, such as a colonoscopy, through their physician.
Dr. Zeynep Gümüş[/caption]
Zeynep H. Gümüş, PhD
Associate Professor
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: The germline genome of each individual person has a unique combination of millions of genetic variants that influence virtually all biological processes throughout life, including cancer evolution. In this study, we have investigated the impact of germline variants – genetic defects one is born with – on gene expression and protein abundance in tumors across cancer types.
MedicalResearch.com: Would you describe the technique of precision peptidomics?
Response: We have leveraged a cohort of 1,064 patients with multiple cancer types to explore the impact of germline variations on cancer-relevant genes through multiple-omics layers: from DNA to RNA, protein abundance and post-translational modifications. To assess the effects of coding variants and their association with cognate proteins, we used precision peptidomics, which is the quantification of peptides carrying genetic variants from individual patients. Through this approach, we mapped 337,469 protein coding germline variants onto patient peptides, revealing their potential impact on protein modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases.
Dr. Sundar[/caption]