PHILADELPHIA – As the American Association for Cancer Research (AACR) Annual Meeting 2025 convenes in Chicago from April 25 to 30, researchers from the University of Pennsylvania’s Abramson Cancer Center (ACC) and the Perelman School of Medicine are poised to unveil pivotal insights that promise to reshape the landscape of cancer biology and therapeutic approaches. These presentations highlight cutting-edge advances in cancer metabolism, immunotherapy, and molecular oncology, reflecting Penn Medicine’s enduring leadership in oncological sciences.
Among the foremost scientific highlights is the work of Dr. M. Celeste Simon, Arthur H. Rubenstein Professor in Cell and Developmental Biology, who will explore the intriguing potential of targeting metabolic pathways as a modality for curing liver and other malignancies. Her talk, scheduled for April 26 in the Discovery Science Plenary session, underscores the growing appreciation of cancer cell metabolism—not simply as a consequence of tumorigenesis but as an active driver and therapeutic vulnerability. Simon’s research delves into how altered metabolic fluxes create metabolic dependencies that can be exploited to selectively eradicate tumor cells without harming normal tissue.
Complementing this metabolic focus, Dr. Shelley L. Berger—a distinguished molecular biologist and recipient of the AACR-Women in Cancer Research Charlotte Friend Lectureship—will deliver a keynote addressing epigenetic regulation and its profound implications for cancer progression and therapy. Dr. Berger’s investigations explore how dynamic chromatin states influence gene expression programs that fuel malignancy. Her pioneering work reveals how epigenetic modulators can be targeted to reverse aberrant transcriptional patterns, thereby restoring cellular controls lost during cancer evolution.
Equally compelling are presentations by Penn’s emerging scientific talents, particularly those centered on the intersection of metabolism and epigenetics in treatment-resistant cancers. Dr. Christina Demetriadou, from Dr. Kathryn E. Wellen’s laboratory, will report findings that elucidate how branched-chain amino acid metabolism contributes to histone propionylation in pancreatic cancer cells. This novel epigenetic modification links nutrient metabolism directly to chromatin remodeling, influencing tumor cell proliferation and survival. Unraveling this metabolic-epigenetic crosstalk offers a promising avenue to disrupt aggressive pancreatic ductal adenocarcinoma, a cancer notoriously refractory to conventional therapies.
In the realm of targeted therapeutics, graduate student Gianna T. Busch will present studies exploring the heterogeneous responses of therapy-resistant melanoma cells to second-line inhibitors. Melanomas harboring the BRAFV600E mutation frequently develop resistance to frontline BRAF inhibitors, prompting the need for innovative combination strategies to circumvent relapse. Busch’s work utilizes high-resolution genetic and phenotypic analysis to identify drug combinations that surmount resistance mechanisms, thereby improving durable responses against this formidable skin cancer.
Adding another dimension to cancer treatment, Margo I. Orlen will discuss breakthroughs in KRAS-targeted therapy in pancreatic cancer models, a domain long hampered by the ‘undruggable’ nature of RAS oncogenes. Orlen’s research, recently published in Cancer Discovery, demonstrates that RAS(ON) multi-selective inhibition not only impairs tumor growth but also reprograms the tumor microenvironment to enhance immune infiltration. By recruiting T cells and other immune effectors, this approach synergizes with immunotherapy, heralding a new paradigm for treating KRAS-driven malignancies.
Penn researchers are simultaneously advancing proteolysis-targeting chimera (PROTAC) technology to promote selective degradation of oncogenic proteins. Postdoctoral investigator Sehbanul Islam will reveal insights into the combinatorial application of VHL and KEAP1-based PROTACs, which show unanticipated synergy and mechanisms that alleviate the ‘hook effect’—a phenomenon that limits PROTAC efficacy at higher concentrations. These findings have fundamental implications for designing next-generation degraders with improved therapeutic windows and specificity.
Radiation oncology is also witnessing transformative innovation at Penn. Premed student Elias El Hoyek will present data demonstrating how FLASH proton radiotherapy—a technique delivering ultra-high dose rates of radiation—significantly reduces corneal damage and accelerates wound healing in murine models. These preclinical results herald a new era in radiotherapy that maximizes tumor eradication while minimizing damage to surrounding healthy tissue, a long-standing challenge in radiation oncology practice.
Bridging immunotherapy and nanotechnology, Dr. Khuloud Bajbouj’s research showcases the engineering of fibroblast activation protein (FAP)-directed CAR T cells via targeted lipid nanoparticles administered in situ. This novel delivery strategy enables robust, localized immune cell activation against the stromal components of pancreatic ductal adenocarcinoma, suppressing tumor progression. Such innovation exemplifies the increasing sophistication of tumor microenvironment-targeted therapies designed to overcome the immunosuppressive barriers erected by aggressive cancers.
In the genetics domain, postdoctoral researcher Mwangala Akamandisa will spotlight the tumor molecular landscape and therapeutic implications in young BRCA1/2 mutation carriers afflicted with breast cancer. These studies shed light on unique genomic profiles and vulnerabilities shaped by inherited mutations, informing tailored clinical management and precision oncology approaches for high-risk populations.
Together, these presentations reflect a broader thematic thrust at the AACR meeting to unravel the complexities of tumor biology through an integrated lens of metabolism, epigenetics, immunology, and therapeutic innovation. Penn Medicine’s contributions exemplify the power of multidisciplinary collaboration and cutting-edge biomedical research to generate transformative knowledge capable of driving next-generation cancer treatments.
The AACR Annual Meeting also provides a platform to honor distinguished leaders in the field. Dr. Shelley L. Berger’s recognition with the Charlotte Friend Lectureship highlights her seminal role in advancing cancer epigenetics and fostering women’s leadership in oncology. Additionally, the election of four Penn cancer researchers to the AACR Academy underscores the institution’s enduring prominence in the cancer research community.
As cancer continues to pose formidable challenges worldwide, the integration of novel scientific discoveries with translational strategies showcased by Penn Medical researchers offers hope for more effective, personalized, and less toxic therapies. The synergy between fundamental biology and clinical application present at this meeting exemplifies the trajectory toward curing cancers once deemed intractable.
In essence, the AACR 2025 Annual Meeting acts as a crucible for pioneering science, uniting researchers, clinicians, and trainees dedicated to decoding cancer’s complexity. The University of Pennsylvania’s robust representation affirms its commitment to transforming academic discoveries into clinical realities, thereby improving outcomes for patients confronting a spectrum of malignancies across the globe.
Subject of Research: Advances in cancer metabolism, epigenetics, immunotherapy, molecular oncology, and novel therapeutic approaches in diverse cancer types including pancreatic, melanoma, liver, and breast cancer.
Article Title: University of Pennsylvania Researchers Unveil Breakthroughs in Cancer Science at AACR Annual Meeting 2025
News Publication Date: April 2025
Web References:
- Abramson Cancer Center: https://www.pennmedicine.org/cancer
- Perelman School of Medicine: https://www.med.upenn.edu/
- AACR Annual Meeting 2025: https://www.aacr.org/meeting/aacr-annual-meeting-2025/
- Shelley Berger AACR Award: https://www.pennmedicine.org/news/news-releases/2025/april/shelley-berger-phd-honored-by-aacr-for-cancer-research
- M. Celeste Simon Profile: https://cdb.med.upenn.edu/people/m-celeste-simon-ph-d/
Keywords: Cancer research, metabolism, epigenetics, immunotherapy, KRAS inhibition, PROTACs, radiation therapy, CAR T cells, pancreatic cancer, melanoma, liver cancer, breast cancer, AACR 2025
