February 2025

Congratulations to TCI members honored in January with endowed professorships:

• Yizhou Dong, PhD - Mount Sinai Professor in Nanomedicine
• Matthew Galsky, MD - Lillian and Henry Stratton Professor of Medicine
• Samir Parekh, MD - Mount Sinai Professor in Cancer Biology

Pictured, left to right: Ramon Parsons, MD, PhD; Brian Brown, PhD; Yizhou Dong, PhD; Samir Parekh, MD; Matthew Galsky, MD; Dennis Charney, MD

Hot off the press: The 2025 TCI Specialty Report

Hideo Watanabe, MD, PhD, received a Lung Cancer Research Program Concept Award from the Department of Defense. His project, “Spatial Copy Number and Morphologic Alterations in Early Lung Carcinogenesis,” will focus on understanding the earliest molecular events in lung cancer development. The goal is to improve early detection and develop diagnostic tools such as molecular tests using blood samples, bronchial brushing or biopsy tissue that complement existing screening methods.

Franco Izzo, PhD, received an ASH Scholar Award in the Basic/Translational Research Junior Faculty category for his project “Defining the Contribution of Epigenetic Plasticity in Resistance to Hypomethylating Agents in Myelodysplastic Syndrome.”

Nina Bhardwaj, MD, PhD, and Mesude Bicak, PhD (Lead Bioinformatician), were awarded grant funding from the Mike Slive Foundation for Prostate Cancer Research for their project, “Harnessing TMPRSS2-ERG Fusion-Derived Neoantigens for an Off-the-Shelf Prostate Cancer Vaccine.” The Foundation funds pilot grants for innovative research that enable investigators to show proof-of-concept.

Nina Bhardwaj, MD, PhD

Mesude Bicak, PhD

Biostatistics



The services of the Tisch Cancer Institute Biostatistics Shared Resource, under the leadership of Madhu Mazumdar, PhD, and Marcio Diniz, PhD, can significantly increase the likelihood of successful grant awards. Researchers are reminded to honor a four-week lead time for grant development. The first step in the process is to submit a service request form. Questions can be directed to Erin Moshier, MSc, Managing Director.

Joshua Brody, MD, and colleagues

Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial

Blood. 2025 Jan 10. PMID: 39792928

This paper reports results from the phase 1b/2 EPCORE® NHL-2 trial evaluating epcoritamab (a CD3xCD20 bispecific antibody) plus Gemcitabine + oxaliplatin (GemOx) in patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had failed autologous stem cell transplant. Results showed that epcoritamab + GemOx yielded deep, durable responses and favorable long-term outcomes.

Press Release

James Asciolla, PhD; Xuewei Wu, PhD; Christos Adamopoulos, PhD; Poulikos Poulikakos, PhD, and colleague

Resistance mechanisms and therapeutic strategies for CDK4/6 kinase targeting in cancer

Nature Cancer. 2025 Jan 30. PMID: 39885369

This review delves into the evolving landscape of CDK4/6 targeting therapies. Dr. Poulikakos and colleagues outline mechanisms of tumor resistance to CDK4/6 inhibitors and highlight novel pharmacologic strategies, including selective degradation and improved targeting of CDK4/6 and CDK2, as well as CDK paralog selective inhibitors and degraders. Emerging roles of CDK4/6 inhibitors in cancer immunotherapy are also discussed, paving the way for new directions in treatment design. Integrating recent discoveries, the review sheds light on new challenges and opportunities for designing more effective CDK-targeting strategies for cancer therapy.

Dmitriy Zamarin, MD, PhD, and colleagues

Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial

Nature Communications. 2025 Jan 9. PMID: 39788967

This phase 1 trial (NCT03738228) explored optimal sequencing of chemoradiation (CRT) and immune checkpoint blockade (ICB)—atezolizumab—in patients with locally advanced cervical cancer (LACC). Findings showed that neoadjuvant ICB prior to CRT (vs. concurrent ICB and CRT) was safe and was associated with immunologically and clinically favorable outcomes. The trend toward superior pathological response, disease-free survival, and tumor-associated T-cell expansion supports further evaluation of the neoadjuvant immuno-oncology treatment and CRT sequencing strategy in LACC.

Osha Rawal, MS; Sacha Gnjatic, PhD; Jeffrey Johnson, PhD; Zeynep H. Gümüş, PhD, and colleagues

PhosNetVis: A web-based tool for fast kinase-substrate enrichment analysis and interactive 2D/3D network visualizations of phosphoproteomics data

Patterns. 2024 Dec 8. PMID: 39010877 

Dr. Gümüş and team present PhosNetVis, a web-based tool for researchers of all computational skill levels to easily infer, generate and interactively explore Kinase-Substrate Interaction networks in 2D or 3D by streamlining phosphoproteomics data analysis steps within a single tool. PhostNetVis lowers barriers for researchers in rapidly generating high-quality visualizations to gain biological insights from their phosphoproteomics datasets. It is available at: https://gumuslab.github.io/PhosNetVis/.

Chrystian Junqueira Alves, PhD; Roland Friedel, PhD, and colleagues

Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2

Nature Communications. 2025 Jan 2. PMID: 39747004

This study demonstrates how glioblastoma (GBM) cells adapt to physical constraints to achieve polarized migration through confined space, thus allowing the diffuse infiltration that contributes to GBM’s high lethality. Findings shed light into the biophysical mechanisms by which guidance receptor Plexin-B2 promotes GBM invasion. These advances in understanding the cellular and molecular underpinnings of the mechanisms of GBM invasion will inform further investigation of mechanosignaling as translational opportunities to curb GBM spread.

Rahat Alam, BS; Gargi Damle, MS; Deniz Demircioglu, PhD; Dan Hasson, PhD; Jerry Edward Chipuk, PhD; Joseph Sparano, MD; Igor Bado, PhD, and colleagues

Bone-Induced Her2 promotes secondary metastasis in HR+/Her2- breast cancer

Cancer Discovery. 2025 Jan 21. PMID: 39835789

This study provides evidence that the bone microenvironment promotes Her2+ circulating tumor cells in metastatic breast cancer patients with initial HR+/Her2- status and identifies a new tumor-promoting circuitry involving NRG3 autocrine signaling that sustains mTOR signaling beyond the osteogenic niche. It also shows that targeting bone-mediated Her2E metastasis impedes secondary dissemination and provides long-term survival benefits. Findings provide insight into mechanisms of resistance that can be transmitted from one organ to another and may help improve diagnosis and guide therapeutic strategies.

Ramy Rahme, MD, PhD; James Manfredi, PhD, and colleagues

Mutant p53 regulates a distinct gene set by a mode of genome occupancy that is shared with wild type

EMBO Reports. 2025 Jan 28. PMID: 39875582

This study shows that wild type p53 may have non-canonical means for regulating gene expression that it shares with a tumor-derived mutant p53. This unexpected molecular finding supports both the gain-of-function and selective loss-of-function that tend to characterize mutant p53 activities in cancer. This has important implications in the prognosis of mutant p53 expression human cancers as well as the development of targeted therapies.

Myvizhi Esai Selvan, PhD; Daniel Nathan, MD; John Mascarenhas, MD; Ronald Hoffman, MD; Bridget Marcellino, MD, PhD; Zeynep H. Gümüş, PhD, and colleagues

Clonal hematopoiesis of indeterminate potential in Crohn's disease and ulcerative colitis

Inflammatory Bowel Diseases. 2025 Jan 6. PMID: 39761417

This study revealed an elevated risk for clonal hematopoiesis of indeterminate potential (CHIP) in older patients with ulcerative colitis and younger Crohn’s disease patients with high clonal burdens, potentially placing them at risk for CHIP-associated complications. Findings prompt clinically relevant hypotheses about the relationship between somatic alterations in hematopoietic cells, inflammation, treatment response, and the risk for malignancy in inflammatory bowel disease (IBD). They provide rationale for the prompt referral of IBD patients with unexplained cytopenias to hematologists for comprehensive evaluation.

Julia Blanter, MD; Deborah Doroshow, MD, PhD, and colleagues

Financial toxicity among patients with advanced solid tumors participating in early-phase clinical trials

JCO Oncology Practice. 2024 Dec. 11. PMID: 39661920

This prospective survey study at Mount Sinai and Yale sought to assess financial toxicity (FT)—which can be a barrier to clinical trial enrollment—among patients with advanced solid malignancies participating in early phase clinical trials (EPCTs).  At the time of consent and 2 months later, patients completed a sociodemographic questionnaire as well as the 11-item validated Comprehensive Score for Financial Toxicity (COST) instrument. Moderate FT was reported at baseline among EPCT participants with no significant difference in COST score between surveys 1 and 2; however, attrition due to disease progression or death prior to survey 2 was significant. Reducing FT associated with participation in EPCTs would maximize access to novel treatments.

Fred R. Hirsch, MD, PhD, and colleagues

Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions

Nature Reviews Clinical Oncology. 2025 Jan 6. PMID: 39762577

This review provides a comprehensive overview of the current landscape of immune-checkpoint inhibitors, the biology that underlies their clinical activity, outstanding research questions and future perspectives on the treatment of patients with advanced-stage squamous non-small-cell lung cancer. 

TCI Seminar Series

Tuesdays at Noon

Davis Auditorium

February 11

Rachelle W. Johnson, PhD, Co-Director, ASPIRE Program in Molecular Medicine, Vanderbilt-Ingram Cancer Center

“Impact of Immune Checkpoint Signaling on the Tumor-Bone Microenvironment"

Hosted by Jose Javier Bravo Cordero, PhD

February 18

Jeffrey A. Hubbell, PhD, Vice President, Bioengineering Strategy, NYU Tandon School of Engineering

“Molecular Engineering Approaches to Cancer Immunotherapy”

Hosted by Yizhou Dong, PhD

February 25

Jalal Ahmed, MD, PhD, Radiation Oncologist, Icahn School of Medicine at Mount Sinai

“Leveraging Radiotherapy to Advance CAR T-cell Therapy for Solid Tumors”

Hosted by Amir Horowitz, PhD

March 4

Diego Chowell, PhD, TCI

Presentation TBD

Hosted by Amir Horowitz, PhD

Dmitriy Zamarin, MD, PhD, is a program organizer of a February 28 CME-accredited webinar on Women’s Malignancies presented by the Society for Immunotherapy of Cancer.

Registration

Registration is open for International School of Immunotherapy, March 10-12. Leading experts in immunology and immunotherapy will share the groundbreaking discoveries made over the past decade. Miriam Merad, MD, PhD, is a course organizer and speaker.

CME-accredited Myeloid Malignancy Workshop

Latest advancements and evidence-based updates in the clinical management of myeloid malignancies

March 21

Davis Auditorium

Course Directors: John Mascarenhas, MD; Marina Kremyanskaya, MD, PhD; Ruben Mesa, MD

Registration (Free Registration Code: JM2025)

Workshop Brochure 

Save the Date

Thanks to all who particpated in World Cancer Day festivities on February 4, providing joy, hope and information for patients and visitors.

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