March 2025

Vladimir Roudko, PhD;   Diane Del Valle, MS; Sacha Gnjatic, PhD, and colleagues

Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer

Journal for Immunotherapy of Cancer. 2025 Feb 25. PMID: 40010771

This work, focused on defining biomarkers of novel immunotherapy treatment, is the first in-depth correlative analysis of an antiangiogenic + checkpoint drug combination in recurrent endometrial cancer. Authors found blood plasma proteins predicting clinical response to combination treatment, with macrophage-related and T cell activation markers associated respectively with poor and improved survival. The implications of the mechanisms unveiled through this study point to developing future treatments that may counteract the negative signals observed while boosting the immunogenicity of the tumor to further improve responses. If confirmed in future studies, the biomarkers defined here would be a potential way to screen for patients more likely to respond to immunotherapy treatment vs. those who may not benefit.

Press Release

Roland Friedel, PhD, was promoted to Professor in the Departments of Neuroscience and Neurosurgery. Dr. Friedel is an internationally recognized expert in axon guidance molecules and brain tumor research.

Friedel Lab



Recent publication in Nature Communications: Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2

John Sfakianos, MD, Associate Professor of Urology and Urologic Oncology, received a 2025 Young Urologist of the Year Award from the American Urology Association (AUA). The award is presented annually to select early-career AUA members in recognition of their commitment to advancing the development of fellow young urologists.

Sarah Ann King, PhD, postdoctoral fellow in the lab of Goutam Chakraborty, PhD, is a recipient of a 2025 AACR Minority Scholar in Cancer Research award. It will fund her participation in the 2025 American Association of Cancer Research Annual Meeting, April 25-30 in Chicago.

Also in Dr. Chakraborty’s lab, Prathiksha Prabhakaraalva, PhD, postdoctoral fellow, received recommendation for funding by the Department of Defense Congressionally Directed Medical Research Program for “Investigating the Impact of Reprogrammed PIK3R1-Insulin-Gucose Metabolism Pathway in Lethal Prostate Cancer to Develop Therapeutic Strategy.”

Jerrel Catlett, 5th year MD/PhD candidate, was selected as a 2025 AACR Minority Scholar in Cancer Research. The award will fund his attendance at the 2025 American Association of Cancer Research Annual Meeting. Jerrel will present his abstract on discovering novel small-molecule therapeutics that recruit previously undruggable E3 ubiquitin ligases to degrade oncogenic proteins as an oral presentation (#3758) on April 28. Jerrel is completing his dissertation work under the mentorship of Jian Jin, PhD.

Raja Flores, MD, Chairman of the Department of Thoracic Surgery, shared the good news that the Department received the highest ranking—“Better Than Expected”—for quality surgery for lung and esophageal cancer from the Society of Thoracic Surgeons, based on publicly reported data.

Biostatistics



The services of the Tisch Cancer Institute Biostatistics Shared Resource (TCI-BSR) can significantly increase the likelihood of successful grant awards. Researchers are reminded to allow a four-week lead time for grant development. The first step is to submit a request for services.

Questions can be directed to Erin Moshier, MSc, Managing Director, TCI-BSR.

The 2024 TCI BSRF Newsletter features accomplishments of the Biostatistics Core in 2024  

Slim Mzoughi, PhD; Ernesto Guccione, PhD, and colleagues

Oncofetal reprogramming drives phenotypic plasticity in WNT-dependent colorectal cancer

Nature Genetics. 2025 Feb 10. PMID: 39930084

This study reveals that colorectal cancer (CRC) cells can revert to a fetal-like state, helping them survive and proliferate despite treatment. The phenomenon, called oncofetal reprogramming, enables some tumor cells to diversify their molecular characteristics and behavior, rendering them resistant to current chemotherapies. Findings propose oncofetal reprogramming as a crucial driver of drug-tolerant states in CRC and indicate that success of the current standard of care treatment hinges on effectively targeting this program. 

Press Release

Josep Llovet, MD, PhD, and colleagues

Human-correlated genetic models identify precision therapy for liver cancer

Nature. 2025 Feb 19. PMID: 39972137

In this study, a set of 25 genetically driven immunocompetent in vivo and matched in vitro hepatocellular carcinoma (HCC) models were developed, recapitulating the 4 human subclasses of HCC, and the therapeutic response to therapies was assessed. Dr. Llovet, Director of the Mount Sinai Liver Cancer Program, and team validated the molecular profiles of these preclinical models against human HCC data—they compared the molecular features from 171 patient-derived HCC samples with the 25 experimental HCC models, correlating them into the four subclasses, and demonstrating the clinical relevance of the models developed in the study. The linkage and alignment of the models with patient data will aid in stratifying patients to treatment and identifying novel therapies.

Emily Bernstein, PhD, and colleagues

ATRX mutations mediate an immunogenic phenotype and macrophage infiltration in neuroblastoma

Cancer Letters. 2025 Jan 30. PMID: 39892705

This study shows that gene expression and cell-state changes resulting from alterations of ATRX—one of the most frequently mutated genes in high-risk neuroblastoma—associate with a characteristic immune cell infiltration in both in vivo models and patient samples. Findings add to the increasing evidence that ATRX mutant neuroblastoma represents a biologically distinct subgroup of patients and provide insight into the mechanisms underlying the distinct clinical phenotype seen in these patients.  

Hideo Watanabe, MD, PhD, and colleagues

Transcriptional regulatory network analysis identifies GRN as a key regulator bridging chemotherapy and immunotherapy response in small cell lung cancer

Journal of Hematology & Oncology. 2025 Feb 5. PMID: 39910394

In this study, Dr. Watanabe and colleagues performed a comprehensive regulatory network analysis and identified granulin precursor (GRN) as a critical regulator associated with resistance to both chemotherapy and immunotherapy in patients with small cell lung cancer (SCLC). Results highlight GRN as a critical regulator of chemo-resistance and a potential biomarker for immunotherapy resistance in SCLC. Targeted therapeutic strategies for GRN-low patients could improve outcomes, while new approaches are needed for GRN-high patients. Overall, the findings implicate GRN as a bridge between chemotherapy and immunotherapy resistance through GRN-mediated mechanisms.

Monika Komza, MS; Jerry Edward Chipuk, PhD, and colleagues

Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival

Cell Communications and Signaling. 2025 Jan 25. PMID: 39863913

This study investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems to provide mechanistic insights into metabolic adaptations. Using a combination of targeted and unbiased metabolomics, real-time bioenergetics analyses, and high-content live-cell imaging in the context of multiple leukemic models, Dr. Chipuk and team dissected the cellular responses to acute glucose uptake inhibition, all of which center on enhanced mitochondrial function. Findings provide insights into the metabolic adaptations and dependencies that arise in leukemic cells under glucose-deprived conditions, presenting potential therapeutic opportunities for clinical interventions.

Criseyda Martinez; Yan Xiong, PhD; Elisa Port, MD; Jian Jin, PhD; Hanna Irie, MD, PhD, and colleagues

A PROTAC degrader suppresses oncogenic functions of PTK6, inducing apoptosis of breast cancer cells

Cell Chemical Biology. 2025 Feb 25. PMID: 39541980

Dr. Irie and colleagues report that MS105, a PTK6 PROTAC degrader, induces apoptosis of breast cancer cells by targeting kinase-dependent and independent functions of PTK6. Findings support PTK6 degraders as a preferred approach to targeting PTK6, an oncogene in breast and other cancer types (prostate, gynecological, liver). Ongoing studies are evaluating the in vivo efficacy of MS105.

Natasha Kyprianou, PhD, and colleagues

Sympathetic nerve signaling rewires the tumor microenvironment: a shift in "microenvironmental-ity”

Cancer Metastasis Reviews. 2025 Jan 20. PMID: 39831934

Dr. Kyprianou and colleagues review the current evidence on the multidirectional impacts of sympathetic nerves and both immune and non-immune tumor microenvironment (TME) components, the nature of these communication processes, and how exploring these interactions may inform future therapeutics to impair cancer progression and metastasis. The studies reviewed emphasize the need to map the spatial profiles of multidirectional interactions within the TME, including the distance-dependent effects of sympathetic signaling. Such quantitative insights will be pivotal in developing computational models to predict the molecular and phenotypic changes resulting from combinatorial treatments. 

Sacha Gnjatic, PhD, will be a panelist on the first in a series of 10 webinars from the Society for Immunotherapy of Cancer on computational science for big data on April 2: “Advanced Biomarker Development and Clinical Translation: Computational Science in Immuno-oncology.”

Edgar Gonzalez-Kozlova, PhD, will be a panelist on the third webinar on May 29: “Lessons from the CIMAC-CIDC Network: Computational Science in Immuno-oncology.”

Registration

Joseph Sparano, MD, gave two presentations at the Miami Breast Cancer Conference, March 6-9—Giants in Cancer Care Lecture: “Tackling Racial Disparities in Breast Cancer,” and “Optimizing Treatment of Node-Negative ER+ Breast Cancer.”

Emily Bernstein, PhD, presented "Epigenetics in Melanoma: Mutations and Mechanisms" at the International Melanoma Working Group in February.

Jerry Edward Chipuk, PhD, gave a keynote lecture at the International Symposium on Mitochondria, Cell Death and Human Diseases: Frontiers in Cancer Research, held in February at Jawaharlal Nehru University in New Delhi. Dr. Chipuk’s talk was titled “A Gated Hydrophobic Funnel Within BAX Binds Long-Chain Alkenals to Potentiate Pro-Apoptotic Function.”

Keynote Speaker: Douglas Wallace, PhD, Children's Hospital of Philadelphia

Registration

TCI Seminar Series

Tuesdays at Noon

Davis Auditorium

March 11

TCI Trainees Research Presentations

• Aliana Guzman – SPARKED Scholar (Mentor: Emily Bernstein, PhD)
• Daniel Nathan, MD – K12 Program (Mentor: Bridget Marcellino, MD, PhD)
• Brendan Berrios – Mentored Medical Student Summer Scholars Program (Mentor: James Ferrara, MD)
• Maryam Ibrahim – TCI Scholar (Mentor: Jerry Edward Chipuk, PhD)

Hosted by Dan Hasson, PhD, and Jerry Edward Chipuk, PhD

March 18

Luca Magnani, PhD, The Institute of Cancer Research, London

“Breast Cancer Dormancy: A Link to the Past”

Hosted by Ernesto Guccione, PhD

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