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[09-October-2023] NEW YORK, Oct. 9, 2023 /PRNewswire/ -- A new combination of treatments safely decreased growth of pancreatic cancer in mice by preventing cancer cells from scavenging for fuel, a new study finds. Led by researchers at NYU Grossman School of Medicine, its Department of Radiation Oncology, and the Perlmutter Cancer Center, the work builds on prior discoveries at NYU Langone that revealed how pancreatic cancer cells, to avert starvation and keep growing, find alternate fuel sources. Normally supplied by the bloodstream, oxygen, blood sugar, and other resources become scarce as the increasing density of fast-growing pancreatic tumors cuts off their own blood supply. In this environment, the ability to switch fuels contributes to the deadliness of pancreatic cancers. Published online October 9 in Nature Cancer, the new study involves a drug designed to prevent pancreatic ductal adenocarcinoma (PDAC) cells from one such switch. PDAC cells use the enzyme glutaminase to convert the amino acid glutamate into glutamine, a form that can be burned for fuel to sustain rapid tumor growth. Drugs designed to block glutaminase, however, have been shown to cause cancer cells to switch to still other scavenging pathways. For this reason, the field next looked at experimental treatments like DRP-104, designed by Dracen Pharmaceuticals, a new "prodrug" form of the compound 6-Diazo-5-oxo-L-norleucine (DON) that is preferentially activated within tumors to overcome toxicity issues seen with DON. DON was designed to starve cancer cells by mimicking glutamine, which unlike glutaminase blockers, broadly inhibits all metabolic pathways that use glutamine. Currently in clinical trials against non-small cell lung cancer, DRP-104 cannot be burned as fuel, but clings to the same enzymes as glutamine. In the current study, DRP-104 treatment alone decreased PDAC growth in mouse models of pancreatic cancer. Importantly, the current team also found that PDAC cells pushed into metabolic crisis by DRP-104 increase signaling through a protein called extracellular signal-regulated kinase or ERK, to make up for their loss of glutamine metabolism. When the team combined DRP-104 with an existing drug that blocks the ERK signaling pathway, trametinib, it further improved survival in pancreatic cancer mouse models compared to DRP-104 treatment alone. "Despite a decade of advances in understanding how cancer cells switch fuel sources, we have not yet effectively translated this into clinically relevant therapies," says corresponding study author Alec Kimmelman, MD, PhD, the Anita Steckler and Joseph Steckler Chair of Radiation Oncology at NYU Langone Health. "Broad antagonism of metabolic pathways with glutamine analogs may provide another mode of attack against these highly resistant tumor cells. The fact that such drugs are already being tested in the clinic makes us hopeful that we may finally see patient outcomes improve, if this approach proves to be effective in clinical trials." Moving forward, the research team will seek to understand how glutamine antagonism impacts other adaptive nutrient scavenging mechanisms in pancreatic cancers and whether these could be targeted as well. The success of such approaches will depend on careful balancing of improved therapeutic efficacy and toxicity from the potential effects on normal tissues, Kimmelman adds. Along with Kimmelman, authors from Perlmutter Cancer Center and the Department of Radiation Oncology at NYU Langone were Joel Encarnación-Rosado, Albert Sohn, Douglas Biancur, Elaine Lin, Victoria Osorio-Vasquez, and Diana González-Baerga. Also Perlmutter authors were Ende Zhao and Diane Simeone. Also authors of the study were Tori Rodrick and Drew Jones from the Division of Advanced Research Technologies at NYU Grossman School of Medicine; Seth Parker from the Department of Biochemistry & Molecular Biology at University of British Columbia in Vancouver, and Yumi Yokoyama and Robert Wild from Dracen Pharmaceuticals, Inc., of San Diego. Funding for the study came from Perlmutter Cancer Center support grant P30CA016087 and National Cancer Institute grants P01A1080192, P01CA117969, R35CA232124, P30CA016087-38, 1R01CA251726-01A1; as well as from the Lustgarten Foundation, Stand Up to Cancer, and the Howard Hughes Medical Gilliam Fellowships. Kimmelman has financial interests in Vescor Therapeutics, is on the scientific advisory board of Rafael/Cornerstone Pharmaceuticals and OncoRev, and has been a consultant for Deciphera and Abbvie. These relationships are being managed according with the policies of NYU Langone Health. Yokoyama and Wild are employees of, and have ownership in, Dracen Pharmaceuticals, maker of DRP-104. Contact: Gregory Williams gregory.williams@nyulangone.org

Predictive Oncology and Cancer Research Horizons partner to drive cancer drugs development. Credit: CDC / Unsplash. Predictive Oncology and Cancer Research Horizons, a part of Cancer Research UK (CRUK), has collaborated to drive cancer drug development using the former’s PEDAL platform. The partnership will use the artificial intelligence (AI) and machine learning platform, PEDAL technology, to determine which cancer types and patient populations are most likely to respond to treatment with Cancer Research Horizon’s pre-clinical drug inhibitors of glutaminase. Predictive Oncology stated that its PEDAL platform makes high-confidence drug response predictions. This helps in more informed drug-tumour type combinations selection for clinical development. By addressing tumour heterogeneity during pre-clinical stages, the platform increases the probability of clinical success. Predictive Oncology CEO Raymond Vennare said: “Our collaboration with Cancer Research Horizons represents a fundamental shift in drug discovery that could lead to the accelerated development of cancer therapies using compounds originating from the CRUK network and developed by Cancer Research Horizons in partnership with their global network. “We now have the ability to impact the most critical stage of early drug discovery in a way that has never been done before.” The company stated that the deal joins non-profit and industry and provides the potential for Cancer Research Horizons to integrate PEDAL technology into the future processes for drug discovery. Cancer Research Horizons and CRUK chief business officer Tony Hickson said: “We are committed to working closely with scientists to discover and advance therapies that can help in the fight against cancer. “Ensuring that patients receive the right treatment for them is of paramount importance and is why we are excited to work with Predictive Oncology to identify the most suitable population for the further development of our compounds.”

EAGAN, Minn., March 17, 2023 (GLOBE NEWSWIRE) -- Predictive Oncology Inc. (NASDAQ: POAI) together with Cancer Research Horizons, the innovation engine at the core of the world’s largest private funder of cancer research, Cancer Research UK (CRUK), today announce that they have partnered to drive the development of oncology drugs utilizing Predictive Oncology’s PEDAL™ platform. “Our collaboration with Cancer Research Horizons represents a fundamental shift in drug discovery that could lead to the accelerated development of cancer therapies using compounds originating from the CRUK network and developed by Cancer Research Horizons in partnership with their global network,” said Raymond F. Vennare, Chief Executive Officer of Predictive Oncology. “We now have the ability to impact the most critical stage of early drug discovery in a way that has never been done before.” The collaboration will utilize Predictive Oncology’s PEDAL technology to evaluate Cancer Research Horizons’ pre-clinical drug inhibitors of Glutaminase in order to determine which cancer types and patient populations are most likely to respond to treatment with these compounds. PEDAL is an artificial intelligence and machine learning platform which makes high-confidence drug response predictions enabling a more informed selection of drug-tumor type combinations for clinical development. PEDAL increases the probability of clinical success by efficiently addressing tumor heterogeneity during pre-clinical stages. “We are committed to working closely with scientists to discover and advance therapies that can help in the fight against cancer. Ensuring that patients receive the right treatment for them is of paramount importance, and is why we are excited to work with Predictive Oncology to identify the most suitable population for the further development of our compounds. We look forward to applying Predictive Oncology’s expertise, enabling technology and dedication to progress exciting cancer therapeutics,” explained Tony Hickson, Chief Business Officer for Cancer Research UK and Cancer Research Horizons. “We consider the potential of this collaboration a win for patients not just in the UK or US, but worldwide.” The agreement bridges non-profit and industry, including revenue sharing for compounds developed and offers the potential for Cancer Research Horizons to incorporate PEDAL into future drug discovery processes. Cancer Research Horizons realizes cancer patient benefit from not-for-profit research and works closely with leading cancer scientists, institutes and companies to protect, develop and commercialize oncology-related discoveries. About Predictive Oncology As a science-driven company on the leading edge of oncology drug discovery, Predictive Oncology (NASDAQ: POAI), offers an unrivaled suite of solutions for the biopharma industry. Through the integration of scientific rigor and machine learning, the company has developed the ability to advance molecules into medicine more confidently by introducing human diversity earlier into the discovery process with the pairing of artificial intelligence and the world’s largest privately held biobank of over 150K tumor samples. Predictive Oncology’s solutions additionally include tumor models, biologics development, formulation design, a GMP facility, a CLIA laboratory and substantial scientific domain expertise. To learn about our partnerships, please go to predictive-oncology.com. About Cancer Research Horizons Cancer Research Horizons is the innovation arm of Cancer Research UK – one of the world’s largest charitable funders of cancer research. We bring together world-leading minds, bold ideas and the right partners to bridge the gap between research and introducing new therapeutics into the market. We focus on the riskier, more profound ideas that can lead to true innovation. By uniting our commercial partnerships and therapeutic innovation capabilities, Cancer Research Horizons is uniquely placed to support translational funding, licensing and collaboration, spin-out creation, and offer a full spectrum of drug discovery and clinical capabilities. With access to Cancer Research UK’s network of 4,000 exceptional researchers, and £300+ million of annual research spend, we’re a powerful partner in the fight to conquer cancer.  Every penny we make goes back into funding the next bold steps, to help bring forward the day when all cancers are conquered. To date, we’ve played an instrumental role in forming over 60 spin-out companies and helped to bring 11 cancer drugs to market. For more information and to get in touch with the team, visit cancerresearchhorizons.com. Contacts Predictive Oncology Theresa Ferguson 1 630 566 2003 tferguson@predictive-oncology.com Cancer Research Horizons Tim Bodicoat tim.bodicoat@cancer.org.uk Predictive Oncology Investor Relations Tim McCarthy LifeSci Advisors, LLC. tim@lifesciadvisors.com Forward-Looking Statements: Certain matters discussed in this release contain forward-looking statements. These forward-looking statements reflect our current expectations and projections about future events and are subject to substantial risks, uncertainties and assumptions about our operations and the investments we make. All statements, other than statements of historical facts, included in this press release regarding our collaboration with Cancer Research Horizons and the potential results therefrom are forward-looking statements. Forward-looking statements also include statements regarding our strategy, future operations, future financial position, future revenue and financial performance, projected costs, prospects, changes in management, plans and objectives of management. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “would,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Our actual future performance may materially differ from that contemplated by the forward-looking statements as a result of a variety of factors including, among other things, factors discussed under the heading “Risk Factors” in our filings with the SEC. Except as expressly required by law, the Company disclaims any intent or obligation to update these forward-looking statements. A photo accompanying this announcement is available at Predictive Oncology partners with the world's largest funder of cancer research to launch PEDAL(TM) Cancer Research Horizons to incorporate Predictive Oncology's PEDAL platform into future drug discovery processes to enable drug development on a global scale.