The Mark Foundation for Cancer Research

Insights from Mark Foundation CEO Ryan Schoenfeld on what last week's news about MRNA vaccines for high-risk melanoma means for the field more broadly: 👇

"At this stage of my career, this fellowship provides an important opportunity to develop the skills and expertise needed to transition towards research independence and establish myself in the critical field of pancreatic cancer research." Martha Zarou is a 2025 recipient of an EACR- The Mark Foundation for Cancer Research Postdoctoral Fellowship, and she has already participated in The Mark Foundation Symposium as well as at the awardee session at this year's EACR Congress - we can't wait to see what she does next. Read more about her fellowship experience so far: https://lnkd.in/eFkzjYFt

When exciting results from the daraxonrasib pancreatic cancer clinical trial were presented recently at the plenary session of ASCO 2026, it was a big moment for a disease with historically few therapeutic options. But in cancer research, the immediate next question is always “how will the tumor fight back?” In a new study just published in Nature Medicine, Ida Aronchik of Revolution Medicines and her co-authors (including The Mark Foundation for Cancer Research grantees Andrew Aguirre and Brian Wolpin from the Dana-Farber Cancer Institute) provide an early answer to that question by studying circulating tumor DNA from patients in the drug's Phase 1/2 trial. Instead of mutating the specific site where the drug binds—a common issue seen with previous generations of RAS-targeting drugs—it turns out that these tumors resisted mainly by increasing the number of mutated gene copies they produce (KRAS amplification) or by switching on backup growth pathways. The researchers then used human and mouse models to test combinations designed to block those specific backup routes. Pairing daraxonrasib with therapies targeting DNA damage response, growth factor receptors, or even companion RAS inhibitors (like zoldonrasib) effectively headed off resistance in the lab. Single-agent targeted therapies are not always a permanent fix for aggressive cancers like pancreatic cancer. By mapping out a tumor's escape routes early, we can design smarter combination treatments that keep patients responding longer. Furthermore, in seeing these mechanisms of resistance to daraxonrasib come to light, I am struck that now more than ever it is a critical time to double down on research towards early detection, diagnosis, and prevention for pancreatic cancer, as well as towards new therapeutic approaches to treating high-risk precancerous lesions. Alongside our partners American Association for Cancer Research and The Lustgarten Foundation, we are proud to support important research along these lines as part of the recently launched Early Detection Award program (https://lnkd.in/gihc9hXH). See below a link to the paper for a great read. Congrats to the team on this excellent work! https://lnkd.in/g7_VJTfn

For years, scientists have been looking for ways to reduce our reliance on traditional 2D cell lines—models that often fail to reflect how complex human tumors behave, mutate, and respond to treatment in actual patients. A trio of landmark papers published in Nature addresses that challenge head-on. An international team of researchers—including Mark Foundation grantees Rebecca Fitzgerald, Owen Sansom, Isidro Cortés Ciriano, Nikhil Joshi, Semir Beyaz, Rameen Beroukhim, Keith Ligon, Andrew Aguirre, James Brenton, Andrea Califano, David Tuveson, Nicolas Robine, and Peter Sorger—has developed a major suite of open-access resources for the global oncology community. Together, these companion papers deliver: 🧬665 next-generation models spanning 25 cancer types, including rare diseases, backed by extensive clinical and genomic data 🧪256 clinically annotated tumor organoids derived directly from colorectal, esophageal, ovarian, pancreatic, and gastric cancer samples 🔬147 genome-scale CRISPR screens and deep multi-omic characterizations across 10 cancer types These models give researchers a much more realistic starting point for research than standard lab samples. Paired with screening data, they offer a powerful new toolkit to uncover new vulnerabilities and develop better-targeted and more effective therapeutics. Huge congratulations to all the authors and institutions involved in this massive undertaking. We’re inspired to see so many scientists from our grantee community helping drive the kind of open, collaborative science we need to change the future for cancer patients. Read the papers in Nature: 📰 https://lnkd.in/ePa7Xd62 📰 https://lnkd.in/gPW4kYwY 📰 https://lnkd.in/gkPnCR8Y

For a long time, the medical world tried to put chronic conditions into neat, separate categories. Cancer in one bucket, heart disease in another, neurodegeneration a third. But as our understanding deepens, it’s becoming increasingly clear how connected many disease processes are, and how many are driven by chronic, low-level inflammation. A great new piece in The New York Times by Kim Tingley nails this shift. What stood out to me most was the spotlight on how aging immune cells (specifically macrophages) can stop doing their job clearing cellular waste and instead end up fueling tumor growth. I was especially pleased to see the work of Miriam Merad, MD, PhD featured in the piece. The Mark Foundation for Cancer Research, the Samuel Waxman Institute for Aging & Cancer, the American Cancer Society, and the Cancer Research Institute (CRI) recently awarded Miriam, Vera Gorbunova, and Nicolas Vabreta grant for their work on a fundamental question: If we can restore the function of aging immune cells, can we improve cancer outcomes, or even prevent disease? https://lnkd.in/gtSnTiK6 Their work is a great example of the kind of bold systems thinking that makes me optimistic about where cancer research is heading. Check out the piece if you haven’t had a chance to read it yet! https://lnkd.in/geGbkn88

For decades, a diagnosis of Diffuse Midline Glioma (DMG) was a near-guaranteed death sentence for children. A recent feature in The New York Times highlights progress—and reminds us why incremental gains aren't enough and why we're so proud to support researchers at the forefront of this field. In 2022, Michelle Monje, featured in this article for her work on DMG biology, co-organized our workshop on pediatric brain tumors at The Banbury Center at Cold Spring Harbor Laboratory. https://lnkd.in/djsCtpC6 Following that workshop, we funded two grants. One went to Srirarm Venneti (also quoted in the article), Elaine Mardis, and Michael Taylor, who are working to identify early biomarkers for Group 3/4 medulloblastoma, another childhood brain cancer. https://lnkd.in/dR8jFZb4 The second grant awarded after the workshop went to Jim Olson & Surojit Sarkar, who are engineering "armored" CAR T-cell therapies specifically designed to overcome the immune-suppressive microenvironment in DMG tumors. https://lnkd.in/dSQiF2GE Separately from the workshop, our Emerging Leader awardee Mariella Filbin is tackling DMG from another critical angle: uncovering how interactions between tumor cells and surrounding neurons drive radiation resistance in young patients. https://lnkd.in/dDjW47EN Every advance in pediatric brain cancer is a win, but giving these children and their families meaningful hope for long, healthy lives will require bold research & funding. We remain dedicated to backing the scientists transforming impossible prognoses into cures. 🎗 🧠 Read the Times article here: https://lnkd.in/dpskAddD

We're proud to support these exceptional postdocs. Please share this opportunity with your network! #ResearchFunding

For a long time, cancer cachexia was treated almost as an afterthought, an inescapable side effect of advanced cancer rather than something we could actively target and treat. That narrative is finally shifting. This week, Amber Dance wrote a terrific feature in Nature looking at how our understanding of cachexia is evolving. We now know it isn't just about malnutrition and muscle wasting. Instead, it's a systemic syndrome involving crosstalk between the brain, metabolism, and immune system. I was glad to share a few thoughts for the piece, including my hope that we are closer than ever to solving this persistent scientific mystery and to finding a way to treat it. What makes me most optimistic is the sheer momentum in the field right now. As the piece highlights, the Cancer Grand Challenges CANCAN team, led by past Mark Foundation grantee Tobias Janowitz, is doing extraordinary work untangling cachexia's drivers. I’m also excited about the work coming out of an ongoing The Mark Foundation for Cancer Research Endeavor Award focused on cachexia. Together, Ayelet Erez, Steffen Jung, Asya Rolls, and Keren Yizhak are exploring the precise neural and metabolic circuits that underpin cachexia. They’ve already made exciting progress, showing that vagal dysregulation disrupts the connection between the brain and liver in cachexia patients, leading to metabolic dysfunction and inflammation. https://lnkd.in/gxM7kdhq Thanks to the collaborative efforts of these researchers and others who work together diligently across disciplines, institutions, and countries, we are closer than ever to real solutions. Worth a read if you want to see where the science is heading: https://lnkd.in/gJqzTAnT

We are deeply saddened by the passing of Joseph Fraumeni, a true giant in oncology. Alongside Frederick Li, his groundbreaking work in 1969 identified Li-Fraumeni Syndrome (LFS), transforming our understanding of hereditary cancer. Dr. Fraumeni’s legacy lives on through the patients who have accessed early detection and treatment thanks to his findings—and in the ongoing research into this devastating condition. At The Mark Foundation, we are proud to support several cutting-edge projects focused on LFS. 🧬 Alongside The Lustgarten Foundation and the American Association for Cancer Research, we are funding work by Trevor Pugh, Brian Crompton, Paul Northcott, PhD, and Kara Maxwell to develop an AI-driven blood test to detect cancers earlier—potentially sparing LFS carriers the burden of constant imaging scans. https://lnkd.in/eGK2JVKy 💊 ASPIRE Awardee Gerard Zambetti of St. Jude Children's Research Hospital is testing a novel compound to prevent cancer in high-risk LFS patients by restoring the function of the mutated p53 protein. https://lnkd.in/eU-PTYqr 🛡️ Women with LFS face an exceptionally high lifetime risk of breast cancer. Research led by Arnold Levine of the Institute for Advanced Study, supported by a 2021 ASPIRE Award, mapped the landscape of immune responses in these tumors, opening the door to more effective, targeted immunotherapies. https://lnkd.in/ewSG9xNR 🤖 Whole-body MRIs are a critical screening tool for children with LFS, but scarce pediatric data have been an obstacle to effective monitoring. Through a 2019 ASPIRE Award, Anna Goldenberg, Andrea Doria, Casey Greene, and Lisa States built synthetic pediatric MRI images to train better models. https://lnkd.in/ecxZrq9x We are proud to support the researchers building on Dr. Fraumeni's remarkable legacy to give LFS patients the long, healthy lives they deserve.

It’s incredibly rewarding this week to see projects The Mark Foundation for Cancer Research has championed from the early stages break out into the mainstream. Three newly published papers from our grantees have been generating a lot of (very well-deserved!) excitement: 1. Moving from early detection to true interception: Last Friday, Charles Swanton and his team’s lung cancer prediction breakthrough made it onto the front page of The New York Times — a true milestone moment! Published in Cell by Cell Press along with colleagues including Tej Pandya, Maria Zagorulya, PhD, Michelle Leung, William Hill, and Clare Weeden, their research identified a 14-protein blood signature that can predict a person’s lung cancer risk more than five years before a diagnosis, whether or not they are a smoker. Instead of catching a tumor that already exists, the signature identifies the underlying inflammatory environment that allows cancer to take hold in the first place. Crucially, the data suggests that an existing anti-inflammatory drug could cut that risk nearly in half for high-risk patients—similar to the cardiovascular disease risk reduction from taking statins. https://lnkd.in/eD-z5ZHw https://lnkd.in/ewUKUxWX 2. A new standard for single-cell multiomics: Also in Cell by Cell Press, Emerging Leader Award winner Dan-Avi Landau debuted a new method to map at the single-cell level how transcription factor proteins turn genes on and off. The method, called "D&D-seq," fuses a targeted nanobody with a deamination enzyme, leaving a permanent chemical footprint exactly where proteins interact with DNA. Because the method captures even highly fleeting, transient interactions and integrates smoothly into existing single-cell workflows, researchers can now map DNA-protein interactions genome-wide. https://lnkd.in/ed9v9cwa 3. Mapping the human purine interactome: In Nature Communications (Nature Portfolio), Emerging Leader Award winner Ku-Lung Hsu built a comprehensive map identifying over 31,000 targetable tyrosine and lysine sites sites across human proteins that could be targeted by future cancer therapeutics. The team has already used this platform to uncover a proteome-wide selective ligand for ACAT2 that reveals an unexpected metabolic dependency in cancer cells. https://lnkd.in/eYUWxxdw When we talk about the strategic value of early-stage, flexible funding, this is exactly what we mean. When you give brilliant investigators the runway to chase audacious ideas, they deliver! Each of these findings gives us new insights into cancer biology and an exciting path to future impact. Congratulations to Charlie, Dan, Ken, and their respective teams on these remarkable achievements!