Roundup: HICCC at AACR 2025

This year, researchers from the Herbert Irving Comprehensive Cancer Center (HICCC) will share their innovative research at the 2025 Annual Meeting of the American Association for Cancer Research (AACR), taking place April 25–30 in Chicago, IL. As one of the premier gathering of cancer researchers from around the world, AACR’s annual meeting showcases the latest advances across the spectrum of cancer science and medicine.

HICCC members are featured across 79 different sessions, including two plenary sessions, five major symposia, five minisymposia, and 58 poster presentations. Their work spans a wide range of topics, including clinical tools, clinical trials, novel therapies, and disparities in oncology. Below are a few selected highlights from this year’s meeting.

Please note: for this roundup, only Columbia researchers and trainees are listed. Please visit the external link for the full listing of authors.

Plenary Sessions

Opportunities in Predictive Oncology

April 30, 2025, 8:05 AM - 8:32 AM CST/ 9:05 AM - 9:32 AM EST

"Quantum cancer therapy: Targeting master regulators of cancer one cell at a time"

Presenter: Andrea Califano, Dr

Andrea Califano, Dr, will discuss new opportunities in predictive oncology, highlighting how network-based approaches like OncoTarget and OncoTreat are driving clinical trials and informing the pharmacologic targeting of tumor subpopulations. He will present his recent findings showcasing how distinct, plastic subpopulations in several cancer types identified through regulatory network analysis can be selectively targeted to develop effective, precision combination therapies. 

AACR Annual Meeting 2025 Highlights: Vision for the Future

April 30, 2025, 12:14 PM - 12:39 PM CST/ 1:14 PM - 1:39 PM EST

"Basic cancer science and translational research"

Presenter: Cory Abate-Shen, PhD

In this plenary session, Cory Abate-Shen, PhD, will highlight notable advances in basic and translational cancer research presented at AACR 2025, offering perspective on how these findings are shaping the future of cancer science. 

Late-Breaking Research

Minisymposium: Late-Breaking Research

April 27, 2025, 4:05 PM - 4:20 PM CST/ 5:05 PM - 5:20 PM EST

"Decoding tumor cell dynamics driven by mutant TP53 gain-of-function activity in squamous cell carcinoma metastasis"

Gizem Efe (presenter), Katherine Cunningham, Raúl Navaridas, Karen Dunbar, Emily Esquea, Carol Prives, Anil K. Rustgi

Major Symposia and Educational Sessions

Lineage Plasticity and Resistance to Cancer Therapy 

April 25, 2025, 3:00 PM - 4:30 PM CST/ 4:00 PM - 5:30 PM EST

“The basics for understanding lineage plasticity in cancer: Insights from studying in bladder cancer” 

Chairperson and presenter: Cory Abate-Shen, PhD 

In this session, Cory Abate-Shen, PhD, will explore the fundamental mechanisms driving lineage plasticity—how cancer cells change identity to resist treatment and promote progression –  focusing on her pioneering work in bladder cancer. Using genetically engineered mouse models and single-cell analyses, her research has identified key transcriptional and epigenetic drivers of these shifts, revealing new vulnerabilities that could be targeted therapeutically.  

Related news: From Bladder Cancer Breakthrough to a Multi-Cancer Pursuit: The Mark Foundation Center for Lineage Plasticity

AACR-Bayard D. Clarkson Symposium: Cellular Plasticity and Heterogeneity in Cancer Progression and Resistance

April 27, 2025, 1:30 PM - 1:50 PM CST/ 2:30 PM - 2:50 PM EST

"Epigenetic regulation of lineage plasticity in castration-resistant prostate cancer"

Presenter: Michael M. Shen, PhD

In this talk, Michael M. Shen, PhD, will highlight emerging insights into the role of epigenetic regulation in driving lineage plasticity and therapy resistance in prostate cancer. Focusing on the histone methyltransferase NSD2, Dr. Shen will share new findings showing how NSD2 promotes neuroendocrine differentiation in castration-resistant disease—and how its inhibition may restore sensitivity to androgen receptor-targeted therapies.

A New Frontier for Combination Therapy: Identification and Pharmacologic Targeting of Malignant Cell States

April 29, 2025, 1:25 PM - 1:45 PM CST/ 2:25 PM - 2:45 PM EST

"Dissecting states and patterns of metastasis"

Presenter: Benjamin Izar, MD, PhD

In this session, Benjamin Izar, MD, PhD, will explore the mechanisms underlying organ-specific metastasis, addressing the fundamental question of why and how cancer cells choose to colonize one organ, such as the liver, over another, like the lung. Drawing on single-cell and spatial multi-omics approaches, Izar will share new insights into the molecular programs and tumor cell states that shape metastatic organotropism, offering potential paths toward therapeutic intervention.

The Interplay Between Nuclear Topology, Gene Regulation, and Cancer 

April 25, 2025, 3:30 PM - 3:50 PM CST/ 4:30 PM - 4:50 PM EST

“Dysregulation of nuclear topology in cancer: Clinical implications and emerging mechanisms” 

Presenter: Aaron Viny, MD 

In this session, Aaron Viny, MD, will present emerging insights into how disruptions in 3D chromatin architecture contribute to cancer development, with a focus on leukemia. He will explore how nuclear topology—shaped by elements like transcription factors, enhancer-promoter interactions, and epigenetic modifications—plays a critical role in regulating gene expression during normal hematopoiesis and how its dysregulation drives malignancy. Viny will highlight recent findings on structural variations and cohesin complex mutations that alter genome organization and fuel leukemogenesis, offering a deeper understanding of the interplay between genome structure and cancer biology. 

The Neuroscience of Cancer 

April 27, 1:30 PM - 1:50 PM CST/ 2:30 - 2:50 PM EST

“Nociceptive neurons promote gastric tumor progression” 

Presenter: Timothy C. Wang, MD

Columbia researchers, led by Timothy C. Wang, MD, have discovered that nerves play a key role in the growth and spread of stomach cancer by releasing neurotransmitters that activate cancer-promoting pathways in tumor cells. In a recent study, they found that blocking these nerve signals with CGRP inhibitors, which are currently used to treat migraines, significantly reduced the size of the tumors, prolonged survival, and prevented the tumors from spreading. Continued research into the connection between the nervous system and cancer could open new possibilities for therapeutic strategies. 

Related research from the Wang lab at AACR:  “The interaction between netrin-1/neogenin modulates sympathetic innervation to promote tumorigenesis and accelerate pancreatic cancer progression”

Synthetic Lethality: What Next? 

April 28, 2025, 1:35 PM – 1:50 PM CST/ 2:35 PM – 2:50 PM EST

“Exploiting dysregulated ribosomal homeostasis in chromosome 9p21.3 deleted cancers and microsatellite unstable cancers” 

Kristina Jankovic, Lucy Parker-Burns, Nicholas Lofaso, Sohani Das Sharma, Riya V. Kishen, Edmond M. Chan (presenter)

Edmond Chan, MD was named a 2025 NextGen Star.

Synthetic lethality is a phenomenon in which changes in two or more genes together cause cell death while changes in one of the two genes alone does not. A promising approach for cancer treatment, several drugs that work by synthetic lethality, such as PARP inhibitors, are already approved by the FDA. A new study, led by Edmond M. Chan, MD, Francisca Vazquez, PhD, and collaborators, used large-scale CRISPR screening to identify PELO, a gene involved in ribosome rescue and mRNA surveillance, as a promising synthetic lethal target in cancers with either large deletions in chromosome 9p21.3 or microsatellite instability-high (MSI-H), both of which are common and associated with poor outcomes. The findings suggest that therapies targeting PELO could be effective across a wide range of difficult-to-treat cancers and that biomarkers like FOCAD deletion or TTC37 mutation could help identify patients most likely to benefit. 

Ferroptosis: From Breakthroughs to Therapeutic Opportunities in Metabolism, Immunity, and Metastasis 

April 30, 2025, 10:20 AM – 10:40 AM CST/ 11:20 AM – 11:40 AM EST

“Ferroptosis and cancer metabolism: History, mechanisms, and therapeutic applications” 

Chairperson and presenter: Brent R. Stockwell, PhD

Ferroptosis is a form of cell death tightly tied with metabolism and driven by peroxidation of specific fats. Brent Stockwell, PhD, will discuss the history and recent research related to ferroptosis, as well as therapeutic applications of controlling ferroptosis, including therapeutic diets. The Stockwell lab identified an unusual species of lipid (fat) that is a key driver of ferroptosis and has linked ferroptosis to metabolism and even found that dietary changes can promote ferroptosis in cancer cells. In addition, they have found that pairing these dietary changes with certain drugs, such as GPX4 inhibitors, can substantially improve therapeutic effects in animal models. 

Mini-Symposia and Workshops

Liquid Biopsy: Circulating Nucleic Acids  

April 28, 2025, 4:05 PM – 4:20 PM CST/ 5:05 PM – 5:20 PM EST

“Association of baseline ctDNA EGFR mutation detection with clinical outcome in the phase II RAMOSE trial assessing ramucirumab plus osimertinib versus osimertinib in EGFR mutant non-small cell lung cancer” 

Catherine Shu and Richard Hall 

While third-generation EGFR inhibitors like osimertinib have improved outcomes in patients with EGFR-mutant non-small cell lung cancer (NSCLC), effectiveness is temporary, and many patients often develop resistance. Primary efficacy results of the phase II RAMOSE trial, for which Columbia was one of the participating sites, shows that a combination of osimertinib with the VEGFR2 antagonist ramucirumab improved progression-free survival (PFS) over osimertinib monotherapy, establishing this regimen as a promising approach to improving clinical outcomes. In this follow-up analysis, researchers explored the identification of baseline EGFR mutation via ctDNA analysis as a potential biomarker for personalized therapy stratifcation. They found that detection of EGFR mutation from blood plasma at baseline was prognostic of clinical outcome, and that detecting EGFR by liquid biopsy can identify patients with higher risk of treatment progression and warrants further investigation for stratification of patients to future clinical trials.   

Continuum of Innovation: Biological Therapeutic Agents 

April 28, 2025, 4:05 PM - 4:20 PM CST/ 5:05 PM – 5:20 PM EST 

"Niche driven inflammatory regulation in the pathogenesis and treatment of myeloid malignancies” 

Pallavi Budgude (presenter), Marta Galan Diez, Abdullah M. Ali, Ziwei Chen, Raul Rabadan, Azra Raza, Stavroula Kousteni

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are blood cancers with limited treatment options and poor patient outcomes. In this study, researchers identified the role of Serum amyloid A1 (SAA1) in  the progression of MDS and AML and showed that antibodies targeting SAA1 could offer a promising new approach to treating MDS and AML by disrupting an inflammatory signal from the microenvironment that drives cancer growth. 

Convergence Science Approaches in Cancer Vulnerabilities Discovery and Treatment Optimization 

April 29, 2025, 3:20 PM - 3:35 PM CST/ 4:20 PM – 4:35 PM EST 

“Single cell transcriptional dynamics in the HCMI cancer model collection” 

Heeju Noh, Luca Zanella (presenter), Andrea Califano

The Human Cancer Models Initiative (HCMI) is a global effort to generate a diverse, accessible library of next-generation patient-derived cancer models—such as organoids, neurospheres, and cell lines—that better reflect the complexity of human tumors. In this study, researchers, including the Califano Lab, analyzed hundreds of HCMI models to assess how closely they mirror their original tumors. Using RNA sequencing (RNA-seq) and single-nucleus RNA-seq, the Califano Lab evaluated the transcriptional fidelity of the models and dissected the regulatory logic underlying tumor-model similarities and potential mechanisms of divergence. They found that most models closely matched their parental tumors in terms of the genetic, transcriptional, and epigenetic features, confirming their value for cancer research and precision drug development. While a small subset (less than 8%) showed divergence due to factors like culture conditions or loss of the tumor microenvironment, these models still preserved most tumor cell states, supporting HCMI’s relevance as a powerful tool for precision oncology.

Related research from the Califano Lab at AACR:  “The landscape of molecular targets across 665 next-generation cancer models in the human cancer models initiative identifies opportunities for improved therapy and overcoming resistance” 

The Local and Systemic Tumor Microenvironment in Cancer Progression 

April 29, 2025, 3:20 PM - 3:35 PM CST/ 4:20 PM – 4:35 PM EST 

“The interaction between netrin-1/neogenin modulates sympathetic innervation to promote tumorigenesis and accelerate pancreatic cancer progression” 

Yosuke Ochiai (presenter), Masaki Sunagawa, Hiroki Kobayashi, Feijing Wu, Jin Qian, Quin T. Waterbury, Biyun Zheng, Yi Zeng, Hualong Zheng, Leah B. Zamechek, Timothy C. Wang

Nerves are known to interact closely with cancer cells and may play a role in helping tumors grow and spread. A protein called Netrin-1 (Ntn1), which helps guide nerve growth during development, has been linked to several cancers—but its exact role in pancreatic cancer isn’t fully understood. In this study, researchers found that Netrin-1 (Ntn1) and its receptor Neogenin (Neo1) are active in pancreatic cancer cells and help tumors grow, spread, and attract nerve fibers. Ntn1 directly promoted cancer cell “stemness” (a trait linked to aggressive growth) and epithelial-mesenchymal transition (EMT), a process linked to cancer spread. Blocking this signaling pathway reduced tumor growth, nerve invasion, and metastasis, and improved survival in mouse models—highlighting Ntn1/Neo1 as a promising target for therapy. 

AI-based Biomarkers and Digital Pathology in Precision Oncology 

April 30, 2025, 5:25 PM - 5:45 PM CST/ 6:25 PM - 6:45 PM EST

"Computational Imaging Biomarkers in Precision Cancer Care: Leveraging Machine Learning and AI for Novel Integrated Diagnostics" 

Presenter: Despina Kontos, PhD 

Despina Kontos, PhD, will lead this session exploring how artificial intelligence and machine learning are transforming cancer care through computational imaging biomarkers, focusing on their integration into personalized diagnostics. With a primary emphasis on breast and lung cancers, her research has pioneered the use of imaging as a quantitative biomarker for improving screening, prognostication, and treatment decisions. Kontos has developed innovative methodologies that extract complex phenotypic signatures from imaging data, providing independent diagnostic, prognostic, and predictive insights. This session will highlight how AI-driven multimodal diagnostic approaches are driving the evolution of precision oncology, offering new avenues for more personalized and effective cancer treatments.