The AACR Grantee Summit 2025: Exemplifying the Innovation AACR Funding Enables

Since 1993, the American Association for Cancer Research (AACR) has invested more than $542 million in grants to sustain the pipeline of cancer researchers and accelerate breakthroughs for patients. The second annual AACR Grantee Summit, held October 5-7 in Philadelphia, offered grantees the unique opportunity to showcase their work and network among peers who, like them, have tirelessly contributed to advancing cancer research with the support of the AACR. 

The summit commenced with an inspiring address by Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “Our grantees are not just recipients of funding, they are catalysts for progress. Every discovery you make brings us closer to preventing and curing cancer,” Foti said. She emphasized the critical role of sustained investment in early-stage ideas and the importance of collaboration across disciplines.

Chairs of the event, Sheila Stewart, PhD, professor in the Department of Medicine at Washington University, and Manuel Hidalgo, MD, PhD, FAACR, professor at the Grossman School of Medicine at New York University, highlighted the ripple effect of AACR grants in their opening remarks. The grants and awards don’t just support projects; they launch careers, foster innovation, and create networks that accelerate breakthroughs, they explained. 

“These are the cohorts of people who will be your colleagues, the ones you turn to for mentorship, for collaboration, for that plasma or that mouse model for your experiments,” Stewart said.

Turning the Guardian into a Guide: TP53 Steps Beyond Prognosis

The summit featured three keynote addresses, a series of thought-provoking panel and roundtable discussions, a lively poster session, and four grantee presentation sessions that showcased the cutting edge of cancer research. The first of the grantee presentation sessions was moderated by Roberto Vargas, MD, a gynecologic oncologist at Cleveland Clinic. Vargas delivered his talk on how TP53, which is a gene that codes for the tumor suppressor protein p53 and is commonly used as a prognostic marker since it is frequently mutated in cancer, could be used to guide therapy for endometrial cancer. 

Vargas pointed out that endometrial cancer is the most common gynecologic malignancy in the United States, and its incidence and mortality are rising sharply. “It is the only cancer where we have failed to improve outcomes over the last three decades,” noted Vargas. His research aims to change that by reframing TP53 mutations as not just prognostic markers but as actionable targets. 

Vargas’ team analyzed how TP53 mutations influence radiation response. Using CRISPR knockouts and complementation experiments, which essentially change how or if TP53 is expressed, Vargas showed that TP53 loss or mutation confers radiation resistance. Vargas also showed in his presentation that introducing mutated TP53 genes into cells that already have the wild-type TP53 suppressed downstream signaling pathways that control cell cycle arrest and DNA repair, making the cells more resistant to radiation.

This means that knowing more about the status of TP53 could guide treatment decisions, particularly in radiotherapy planning. Vargas also explored therapeutic angles, testing MDM2 inhibitors, which are molecules that prevent the protein called MDM2 from binding to p53, alongside radiation treatment. Normally, MDM2 acts like a regulator, keeping p53 levels low by tagging it for destruction by large protein complexes called proteasomes. When MDM2 is inhibited, p53 can stay active and perform its tumor-suppressing role. He explained that using MDM2 inhibitors showed promise in wild-type settings, but they fell short in high-grade TP53-mutant tumors. 

Vargas and his team are now looking at alternative pathways like p63 and p73 signaling to obtain a response in these high-grade TP53 mutants. p63 and p73 are members of the same protein family as p53 and share similar DNA-binding domains, meaning they can activate many of the same genes involved in cell cycle arrest and apoptosis. By targeting or enhancing p63 and p73 activity, Vargas hopes to bypass the defective p53 and restore sensitivity to radiation. “We may be able to exploit these pathways to develop new radiosensitizing strategies,” he said. 

Vargas’ work on moving TP53 from a static marker to a dynamic tool for therapy selection shows that innovative ideas can shift how existing tools in cancer can be repurposed to be better and far more effective.

Radiation’s Plot Twist, Where Pain Relief Might Work Against You

The second grantee presentation session was moderated by Igor Bado, PhD, assistant professor at the Icahn School of Medicine at Mount Sinai, who presented his work titled “Determining FGF2-mediated DTC fate in breast cancer bone metastasis.” DTCs, or disseminated tumor cells, are cells that leave the primary tumor, circulate through the blood, and enter another site, often causing metastasis. Bado discussed the factors that determine when DTCs stay dormant or proliferate. His research focused specifically on breast cancer DTCs that entered bone.  

“Breast cancer metastasis to bone remains a major clinical challenge, often leading to incurable disease,” Bado said. His team focused on fibroblast growth factor 2 (FGF2), a molecule that binds to components of the bone matrix for stability. This stability means FGF2 can continuously signal to cancer cells, creating a supportive niche for their survival and growth. Using multiplex imaging and in vivo models, they mapped FGF2-rich niches and found that areas with high FGF2 deposition harbored proliferating cancer cells.

Bado noted that radiation therapy, which is commonly used for pain management in bone metastasis, added another layer of complexity. “Irradiation boosted FGF2 expression and disrupted its normal distribution,” Bado explained. This means that the therapeutic stress of radiation therapy might inadvertently promote metastatic growth. He presented findings that showed how FGFR inhibitors reversed these effects in preclinical models, pointing to a potential intervention strategy. 

Bado’s work on revealing how tumors and treatments reshape the bone niche opens doors to therapies that could prevent metastatic outgrowth and help improve long-term survival in breast cancer.

Pinning Down TFE3: A Molecular Trap for a Rare Kidney Cancer’s Master Switch

Srinivas Viswanathan, MD, PhD, a medical oncologist at the Dana-Farber Cancer Institute, and moderator of the third session of grantee presentations, showcased work that focused on translocation renal cell carcinoma (TRCC). TRCC is a rare, and aggressive cancer that grows in the kidney and is driven by TFE3 gene fusions, which means the TFE3 gene breaks apart and joins with another gene, creating a hybrid that produces an abnormal protein that promotes cancer cell proliferation. 

“There are no approved therapies that directly target this biology,” Viswanathan noted. 

His team’s goal was to find small molecules that inhibit TFE3 function. They screened 25,000 compounds and identified a molecule called BRD6866 that traps TFE3 on chromatin. 

“We often think about evicting transcription factors, but trapping may be an equally powerful way to shut them down,” Viswanathan said. For TRCC patients, this research offers hope for targeted therapies where none exist. 

Exploiting the Tiny Changes When Tumors Hold Their Breath

Min Yu, PhD, professor at the University of Maryland, who was the moderator of the final grantee presentation session, presented her talk on “Prolonged suppression of tumor intrinsic interferon signaling on metastasis,” which explored a concept called “hypoxia memory.” Hypoxia, which is low levels of oxygen in the body’s tissues, is a ubiquitous property in the tumor microenvironment, especially in solid tumors.

According to Yu, tumor cells exposed to low oxygen don’t just adapt temporarily, they undergo permanent changes that promote metastasis. Yu and colleagues traced this effect to lactate accumulation and histone lactylation, an epigenetic modification. “Lactate is not just a metabolic byproduct; it’s also a signaling molecule,” she explained.

In vitro experiments by Yu and her team showed that adding lactate alone could mimic cell hypoxia, silencing interferon pathways and enhancing metastatic potential. Her work showed that histone deacetylase (HDAC) inhibitors, which are drugs that block the enzymes that normally remove chemical tags (including lactate) from histones, reversed these changes, showing future therapeutic potential. 

Yu also examined immune landscapes in metastatic sites, finding shifts in macrophage populations and systemic changes in the spleen. While these data are preliminary, Yu explained that they suggest that hypoxia memory influences both tumor-intrinsic and -extrinsic factors.

The AACR Grantee Summit represents not just the novel discoveries and innovative ideas that will shape the landscape of cancer research, but also the people that drive such work: the investigators, the funding partners, mentors and mentees, and all other stakeholders. It showcased what happens when innovative ideas meet sustained support.  

As Foti remarked, “Every grant is an investment in hope, and today, we saw that hope in action.”