Roundup: HICCC at AACR 2024

HICCC Researchers Present at American Association for Cancer Research Annual Meeting

April 2, 2024

Thousands of researchers, clinicians, patients, and health advocates will be attending the AACR Annual Meeting this week, held April 5 to 10 in San Diego, CA. With over 50,000 members, the AACR is one of the largest professional organizations dedicated to cancer research in the world, and their annual meeting is one of the largest in the country for the cancer research community. Dozens of HICCC members will be attending and presenting their innovative research at this year’s meeting and will be recognized for their significant scientific contributions in the field of cancer research.  

Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Anil K. Rustgi, MD

Anil K. Rustgi, MD, stands at a podium giving a presentation at the 2024 AACR Annual Meeting.

Anil K. Rustgi, MD was honored with this year's Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research.  (Photo credit: 2024 AACR/Todd Buchanan)

Anil K. Rustgi, MD, has been named as this year's recipient of the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research. Dr. Rustgi's relentless dedication to fostering the growth and development of cancer scientists and physicians at all career levels has earned him this prestigious recognition.

As the Herbert and Florence Irving Director of the Columbia University Herbert Irving Comprehensive Cancer Center and chief of cancer services at NewYork-Presbyterian Hospital, his visionary leadership has not only shaped the education and training landscape but has also empowered countless individuals to embark on successful careers in cancer research.

Dr. Rustgi's commitment to mentoring undergraduate, graduate, medical, and doctoral students, as well as clinical residents, fellows, and faculty members, exemplifies his unwavering passion for advancing the field. His award lecture, scheduled for Sunday, April 7, at 3 p.m. PT, will focus on gastrointestinal cancer metastasis and the role of tumor suppressor genes, such as p53, a focus of Rustgi's research.

Research Highlights

HICCC members will present their research on more than 50 different sessions, including one major symposia, seven minisymposia, and 47 posters. Topics will range from clinical tools, clinical trials, therapies, disparities in oncology and more. Below are a few selected research highlights. 

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

Late-Breaking Research

Late-Breaking Research: Tumor Biology 1

April 8, 2024, 1:30 PM- 5:00 PM

"Novel organoid models of lineage plasticity in castration resistant prostate cancer"

J. Lu, M. M. Shen

This study investigates epigenomic mechanisms driving aggressive neuroendocrine prostate cancer (CRPC-NE), a subtype of metastatic castration-resistant prostate cancer (mCRPC). The findings suggest a promising therapeutic avenue for patients with CRPC-NE and pave the way for further exploration of epigenetic-targeted therapies in prostate cancer management.

Minisymposium: Late-Breaking Research

April 8, 2024, 3:35 PM- 3:50 PM

"Prrx1 regulates acinar cell plasticity via TGFβsignaling in pancreatic acinar-to-ductal metaplasia"

N. Nishiwaki, K. Sugiura, A. Li, K. SuzukiJ. R. Pitarresi, R. Chandwani, A. K. Rustgi

This study investigates the role of a transcription factor called Prrx1 in two types of cellular transformations in the pancreas: adaptive acinar-to-ductal metaplasia (ADM) and oncogenic ADM, which can lead to pancreatic cancer. The findings shed light on the molecular mechanisms underlying pancreatic cancer development and suggest Prrx1 as a potential therapeutic target for intervention.

Advances and Major Symposia

Methods Workshop: Choosing the Right Animal Model for Your Study

April 6, 2024, 12:30 PM - 2:00 PM

"The A, B, Cs of modeling cancer in genetically engineered mouse model"

Presenter: Cory Abate-Shen, PhD

This session will focus on some of the cardinal features one might want to study in cancer immunology, some of the tradeoffs for using different models to address these questions, and opportunities that are provided by genetically engineered models for studying complex biologies like impact of a native tumor microenvironment and tumor associated tertiary lymphoid structures (TLS). 

Advances in Diagnostics and Therapeutics: Oligometastasis- Curable Metastatic State?

April 7, 2024, 1:05 PM - 1:25 PM

"Defining the oligometastatic state: mechanisms and biological determinants"

Presenter: Catherine S. Spina, MD, PhD

This session will explore our current understanding of the spectrum of metastatic cancer and how we define low volume metastatic disease or the “oligometastatic state.” 

Systematic Functional Approaches for Understanding and Targeting Cancer

April 8, 2024, 11:00 AM - 11:15 AM

"Functional and computational approaches to uncover selection advantages of cancer aneuploidy"

Presenter: Alison M. Taylor, PhD 

This study investigates the role of aneuploidy, or chromosome abnormalities, in cancer development. Through analyzing data from thousands of patient tumors, researchers identified specific patterns of chromosome alterations associated with different cancer types. This analysis also helped identify important genes driving these large chromosome alterations. Using CRISPR-Cas9 genome editing, they explored the impact of these alterations in lung cancer, observing changes in gene expression and cell behavior. Furthermore, by culturing cells as organoids, they demonstrated how these chromosome alterations affect cell differentiation, providing valuable insights into cancer progression and potential therapeutic targets.

Major Symposium: Disparities in Pediatric Oncology

April 8th, 2024, 12:30 PM - 2:00 PM

Panelist: Justine Kahn, MD 

This special session spotlights pediatric cancer disparities, delves into underlying mechanisms, and suggests system and policy changes to address them. 

Early-Onset Cancers: Challenges and Opportunities for Prevention and Treatment

April 9, 2024; 10:40 AM - 11:00 AM

"Early-onset breast cancer: What we have learned from enriched cohorts that may inform the global trends"

Presenter: Mary Beth Terry, PhD

This session aims to cast a spotlight on the rising incidence of early-onset cancers and forge a path forward. The session will highlight advances in risk factor identification, molecular signatures, mechanistic understanding, and treatment of early-onset cancers, using colorectal cancer and breast cancer as exemplars.



April 7, 2024, 3:05 PM - 3:20 PM 

"p53-R172H mutation confers gain-of-function properties and promotes metastasis in squamous cell carcinoma"

G. Efe, K. Cunningham, R. Navaridas Fernandez de Bobadilla, K. J. Dunbar, K. Sugiura, N. Nishiwaki, A. M. Taylor, C. Prives, A. K. Rustgi

In this research from the lab of Anil Rustgi, MDthe team demonstrated that gain-of-function mutant p53-R172H, but not wild-type p53 binds to the epigenetic reader bromodomain and extra-terminal motif (BET) protein BRD4 to regulate CSF-1 transcription, promoting esophageal squamous cell carcinoma (ESCC) metastasis through STAT3 phosphorylation and epithelial-to-mesenchymal transition (EMT). These results will hopefully have implications in therapeutic approaches for metastatic ESCC cases, as well as for other squamous cell carcinoma patients whose tumors share similar genomic and epigenetic features.

Multi-omic Analysis and Translational Research

April 8, 2024, 3:05 PM - 3:20 PM

"Adaptive heterogeneity enables the survival of residual malignant PDAC cells in response to RAS-GTP inhibition"

L. Tomassoni, U. N. Wasko, A. C. Garcia, T. C. Dalton, P. Laise, S. A. Sastra, C. F. Palermo, A. Califano, K. P. Olive

Tomassoni and colleagues (the lab of Andrea Califano, Dr) have been studying how a new class of RAS inhibitors may be used to treat pancreatic cancer, and how those tumors might eventually develop resistance. They focused on the earliest days of treatment to understand how malignant pancreatic tumor cells immediately respond to treatment. They found that some tumor cells can transiently adapt to the treatment, buying them time to eventually develop new resistance mutations. Understanding how different malignant cells initially respond to treatment may provide a path towards the development of multi-drug regimens prevent the development to drug resistance.

Immune Targets and Therapies

April 8, 2024, 3:20 PM - 3:35 PM

"A CXCR4 partial agonist TFF2-MSA improves anti-PD-1 immunotherapy in advanced gastric cancer by selectively targeting PMN-MDSC"

Jin Qian, Quin T. Waterbury, Christine S. Moon, Xiaofei Zhi, Feijing Wu, Ruhong Tu, Biyun Zheng, Hiroki Kobayashi, Leah B. Zamechek, Ryan H. Moy, Arnold Han, Timothy C. Wang

Advanced gastric cancer presents a challenge for current immunotherapy, particularly due to the presence of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) expressing high levels of CXCR4. This research from the lab of Timothy Wang, MD introduces a promising approach by combining a novel CXCR4 partial agonist, TFF2-MSA, with PD-1 blockade. The preclinical research reveals that this combination therapy effectively targets and reduces CXCR4high PMN-MDSCs in vivo, leading to significant tumor regression and improved survival rates in preclinical mouse models. These findings hold potential for developing more effective treatment strategies for advanced gastric cancer patients resistant to conventional immunotherapies.

Application of Real-World Evidence to Cancer Care

April 8, 2024, 3:35 PM - 3:50 PM

"Comprehensive molecular and immunological characterization of early-onset esophagogastric cancer"

L. W. Wu, R. H. Moy

There has been a marked rise in the onset of early-onset esophagogastric cancer over the past several decades without a clear explanation. The team (including Ryan Moy, MD, PhD) used the Caris Life Sciences database to study over 5000 patients with esophagogastric cancer. We compared patients under age 50 years to patients over age 50 years old. They found several molecular features of early onset esophagogastric cancer may make these younger patients less likely to respond to current immunotherapy and other standard of care treatments for esophagogastric cancer. They also identified a set of molecular changes that may represent potential therapeutic opportunities for treatment in this patient population. These findings may catalyze additional investigations for this patient population.

Computational Approaches to Precision Medicine

April 9, 2024, 3:05 PM - 3:20 PM

"Reversing lineage plasticity and drug resistance in lethal prostate cancer"

A. Vasciaveo, J. J. Li, D. Karagiannis, X. Chen, A. Califano, C. Lu, M. M. Shen

Recent studies have demonstrated that cancer cells can employ adaptive mechanisms, rather than solely relying on mutations, to evade targeted therapies. A team from the labs of Michael Shen, PhD and Andrea Califano, Dr utilized genetically-engineered mouse models of prostate cancer to investigate how tumor cells respond to treatment with enzalutamide, a standard therapy for castration-resistant prostate cancer (CRPC). By analyzing single-cell data from mouse organoids, they identified various cell populations, including those undergoing neuroendocrine differentiation, which are resistant to enzalutamide. Furthermore, the study pinpointed a potential therapeutic target, NSD2, whose inhibition restored sensitivity to enzalutamide in these resistant cells, highlighting a promising avenue for future therapeutic interventions in lethal prostate cancer.