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Researchers from Â鶹ӳ»­ MD Anderson Cancer Center will present promising results from clinical trials in three minisymposia abstracts at the . Findings include a personalized vaccine combination therapy for colorectal cancer, the use of radiotherapy to avoid the toxicities of systemic treatments for kidney cancer, and engineered exosomes to silence mutant KRAS in pancreatic cancer.

In addition to these trials, forthcoming press releases will feature notable oral and plenary session abstracts. More information on all MD Anderson AACR Annual Meeting content can be found at .

Personalized vaccine with or without immunotherapy is safe for patients with metastatic colorectal cancer subtype (Abstract )
Patients with microsatellite-stable metastatic colorectal cancer?(MSS mCRC) have poor outcomes and limited treatment options after failure of standard chemotherapy, in part because of an immunologically ¡°cold¡± tumor microenvironment. Researchers led by , and , developed a personalized vaccine platform called NeoAg-VAX that uses bioinformatics and sequencing tools to deliver up to 10 tumor-derived proteins targeted to each patient¡¯s specific combination of mutations. In this Phase I feasibility study, the researchers combined the personalized vaccine with and without pembrolizumab immunotherapy?in 28 patients with MSS mCRC. The personalized vaccine was safe and feasible to administer, leading to strong immune responses in most patients vaccinated on this study.?The researchers also characterized immune cell composition within patients' tumors,?providing molecular insights into the immune microenvironment that could inform future therapeutic approaches. Haldar will present the results April 27.

Metastasis-directed radiation therapy avoids toxicities of systemic therapy in patients with clear cell renal cell carcinoma (Abstract )
Systemic therapies used for patients with metastatic clear cell renal cell carcinoma (ccRCC), such as immunotherapy and tyrosine kinase inhibitors, are associated with high toxicity rates. Metastasis-directed radiation therapy may limit side effects, but there are no established biomarkers to identify patients most likely to respond. Therefore, researchers led by , and , conducted a Phase II prospective trial investigating metastasis-directed therapy without systemic therapy in 121 patients with oligometastatic ccRCC. The median progression-free survival (PFS) was 18 months, with a median of 34 months systemic therapy-free survival (STFS). Importantly, overall survival (OS) was not compromised, with OS rates of 94% and 87% at two and three years, respectively. The researchers also tested a novel tumor-informed circulating tumor DNA (ctDNA) assay to detect molecular residual disease (MRD). Patients who were MRD- versus MRD+ at baseline had median STFS of 54 months compared to 27 months. These findings show that metastasis-directed radiation therapy can help patients avoid systemic therapies without compromising outcomes and that the ctDNA assay is a useful personalized prognostic biomarker for response. Tang will present the results April 28.

Exosomes deliver gene silencers for KRAS G12D pancreatic cancer (Abstract )
KRAS G12D mutations occur in over 40% of pancreatic cancer cases, but KRAS inhibitors have not yielded durable responses for patients, partly due to an immunosuppressive tumor microenvironment. Exosomes are small extracellular vesicles that can be engineered to carry small interfering RNA (siRNA), which silence specific genes, into cancer cells. In a first-in-human Phase I dose escalation trial, researchers led by Valerie LeBleu, M.D., Ph.D., , , and , examined the use of engineered exosomes derived from bone marrow cells to silence KRAS G12D in 12 patients with metastatic pancreatic cancer. Six of the 12 patients receiving all exosome doses had stable disease in target lesions, and there were no dose-limiting toxicities. The researchers noted a reduction in KRAS G12D circulating DNA post-treatment. Further in vivo analysis revealed that these exosomes would work well with immune checkpoint blockade to reprogram the tumor microenvironment and overcome treatment resistance, highlighting the combination as a potential therapeutic strategy being investigated in an upcoming Phase II trial. LeBleu will present the results April 29.

In addition, Abstract ?features early clinical trial data from the ATR kinase inhibitor, ART0380, in advanced solid tumors. This targeted therapy was initially discovered and developed by MD?Anderson¡¯s Therapeutics Discovery division?and licensed?to Artios Pharma. Preclinical and translational studies led by investigators at MD Anderson, published in , demonstrated potent antitumor activity and established an innovative approach to optimize patient selection based on molecular tumor features.

CHICAGO ¨D?, chair of?Bioinformatics and Computational Biology?and professor of?Systems Biology?at Â鶹ӳ»­ MD Anderson Cancer Center, has been elected to the 2025 class of??in recognition of decades of combined laboratory and computational work pioneering multi-omic molecular profiling, including the introduction of new laboratory techniques, clustered heat maps, and early innovations in artificial intelligence for cancer drug discovery.

The mission of the??is to honor distinguished scientists whose contributions have propelled significant progress and breakthroughs against cancer.?Weinstein is part of a select cohort of 33 distinguished scientists, rigorously reviewed and chosen by the AACR Academy for their exceptional contributions driving innovation and progress against cancer.

Weinstein joins 15 previously elected fellows from MD Anderson, including current members,?,?,?,?,?,?Margaret L. Kripke, Ph.D.,?,?,?, and Louise C. Strong, M.D. Former members, now deceased, include Isaiah J. Fidler, D.V.M., Ph.D., Emil J Freireich, M.D., Waun Ki Hong, M.D., V. Craig Jordan, Ph.D., and John Mendelsohn, M.D.

¡°Dr. Weinstein has made substantial contributions to advancing our knowledge of the molecular profiles of cancer, and we celebrate his recognition as a Fellow of the AACR Academy,¡± said?Peter WT Pisters, M.D., president of MD Anderson. ¡°His crucial data science work includes the creation of countless analytical tools that help translate breakthrough discoveries into clinical advances that improve the lives of patients.¡±

Weinstein earned a B.A. in Biology, a Ph.D. in Biophysics and an M.D. from Harvard University, and he completed his internship and residency in Medicine at Stanford University. Throughout his career, he led hybrid laboratory and computational research groups, and, since the early 1990s, he has focused on integrative multi-omic studies and issues of data quality control. At the National Cancer Institute (NCI), he headed the Genomics and Bioinformatics Faculty and a computational Immunology section.

Since 1991, Weinstein¡¯s research has focused on molecular profiling of cancer with an emphasis on drug discovery. In 1992, he began characterizing the NCI-60 human cancer cell lines at the DNA, RNA, protein and epigenomic levels ¨C the first large multi-omic profiling project ¨C which provided a design template for the??and??projects, as well as contributing to some major aspects of??(TCGA) project and its descendants.

One of Weinstein¡¯s many analytical tools, the color-coded clustered heat map (CHM), provides an intuitive visualization of patterns in complex biological data. This tool led to the clinical development of oxaliplatin, a chemotherapy drug that has become a standard component of treatment for colorectal, pancreatic and other cancers. The CHM became a ubiquitous form for visualization of -omics data, and Weinstein is now introducing artificial intelligence to improve its characteristics as a dynamically interactive next-generation CHM.

His work overall has contributed to the ¡°Findable, Accessible, Interoperable and Reusable (FAIR)¡± principles of Data Science, established guidelines for managing and sharing research data to maximize their potential value and facilitate discovery.

¡°Dr. Weinstein is an exemplary leader in the field of bioinformatics, and his discovery work has generated tremendous lasting benefits for the scientific community,¡± said?, chief scientific officer at MD Anderson. ¡°We are proud to have him as part of our MD?Anderson research community, and he joins an incredible group of scientists in the AACR Academy.¡±

In 2008, Weinstein was recruited to MD Anderson to build the Department of Bioinformatics and Computational Biology, which he still chairs. He also serves as a scientific advisor to MD?Anderson¡¯s Proteomics, Functional Proteomics Reverse Phase Protein Array (RPPA), Metabolomics and Single Cell Genomics Cores. Since 2009, he has been a principal investigator of MD Anderson¡¯s NCI Genome Data Analysis Center, and he served for 18 months as chair of the NCI TCGA Network Steering Committee. He is a founding affiliate member of MD Anderson¡¯s?Institute for Data Science in Oncology?and serves as director of the?Bioinformatics Shared Resource.

Weinstein was awarded the Hubert L. Stringer Chair for Research in 2015 and has received STARS and STARS-PLUS awards from Â鶹ӳ»­ at Austin, as well as a Cancer Prevention and Research Institute of Texas (CPRIT) Core Grant for proteomics and metabolomics. He has received generous funding from The Mary K. Chapman Foundation and Michael and Susan Dell Foundation. With more than 400 publications ¨C including 14 first-author publications in?Science?or?Nature?¨C and over 150,000 literature citations, Weinstein was recognized as ¡°a highly cited researcher of the decade¡± by the Web of Science in 2020.

More information on all MD Anderson AACR Annual Meeting content can be found at?.?