September 2025

Adolfo Aleman, PhD, MPA; Oliver Van Oekelen, MD, PhD; Patrick Brunner, MD; Joshua Brody, MD; Samir Parekh, MBBS, and colleagues

Targeted Therapy of CAR+ T-Cell Lymphoma After Anti-BCMA CAR T-Cell Therapy

New England Journal of Medicine. 2025 Aug 21. PMID: 40834307

This paper highlights the first reported case of successfully using targeted therapy for a rare and aggressive T-cell lymphoma that developed after CAR T-cell therapy for multiple myeloma. Following advanced genetic and immunologic screening, the patient received treatment with the anti-CCR4 antibody mogamulizumab in combination with liposomal doxorubicin and gemcitabine; the treatment led to complete remission. The positive results in this case show that treatment based on genomic, phenotypic, and functional profiling can provide an effective therapeutic strategy in similar rare but serious cases.

Press Release

Molecular follow-up studies will be featured as a top oral presentation at the 2025 Annual Meeting of the International Myeloma Society, September 17-20: “TET2 and EZH2 Genetic Alterations Promote Malignant CAR-T Transformation in Anti-NCMA CAR-T Therapy,” presented by Adolfo Aleman, PhD.

The International Association for the Study of Lung Cancer (IASLC) presents annual awards to clinicians and researchers who have made significant contributions to the fight against lung cancer. At the 2025 IASLC World Conference on Lung Cancer, held September 5-9 in Barcelona,

• Andrea Wolf, MD, MPH (Thoracic Surgery), received the Robert J. Ginsberg Lectureship Award for Surgery. She presented her lecture, "Tailoring Therapy for Pleural Mesothelioma," at the Plenary Session on September 7.

• Mary B. Beasley, MD (Pathology), received the Fred R. Hirsch Lectureship Award for Translational Research. The title of her lecture, presented at the Plenary Session on September 9, was “The Future of Pathology in Translational Research.”

Andrea Wolf, MD

Mary B. Beasley, MD

Saad Atiq, MD, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology). He sees patients with genitourinary cancers, particularly prostate and bladder cancers, at the Ruttenberg Treatment Center. Dr. Atiq completed his residency in Internal Medicine at Duke University Medical Center and a fellowship in Medical Oncology at the National Cancer Institute (NCI). He earned his MD from the University of Arkansas for Medical Sciences. Dr. Atiq has been an associate investigator on numerous NCI clinical trials for genitourinary malignancies. He was selected for the 2023 Bladder Cancer Advocacy Network’s John Quale Travel Fellowship Award. He also received a National Institutes of Health Award for Research Excellence and the NCI Herb Kotz Award for Excellence in Oncology, both in 2024. 

Dan Filipescu, PhD, in the Bernstein Laboratory, was awarded R03 funding from the National Cancer Institute for “Epigenetic Regulation of Melanoma-Associated Fibroblast Plasticity.” Dysfunction of histone variants contributes to cancer, either by driving abnormal gene expression programs in malignant cells, or by reprogramming non- malignant cells of the tumor microenvironment. Using cancer-associated fibroblasts derived from human melanoma coupled with advanced epigenomic techniques, this project aims to dissect the role of macroH2A histone variants in regulating pro-inflammatory signals produced by cancer-associated fibroblasts. The studies will elucidate how macroH2A shapes the tumor microenvironment to potentially impact melanoma initiation, response to therapy, progression, recurrence, and/or dormancy.

Anindita Dutta, PhD in the Arriaga Lab received an Early Investigator Award from the Department of Defense for “To Investigate Tumor-Intrinsic Epigenetic Mechanisms Modulating Antitumor Immune Responses in Metastatic Prostate Cancer.” This project, focused on metastatic castration-resistant prostate cancer, aims to delineate the epigenetic regulatory pathways that facilitate tumor-mediated immune evasion and restore effective antitumor immunity. The ultimate goal is development of targeted epi-immunotherapeutic approaches to potentiate immune responsiveness and improve therapeutic outcomes in advanced prostate cancer.

Emanuel Taioli, MD, PhD, was awarded R21 grant funding from the National Cancer Institute for

“Update of the WTC Cancer Tissue Biobank.” The biobank provides the infrastructure to address questions related to cancers in World Trade Center responders, such as the link between specific carcinogens and cancer types, molecular signatures of exposure that could be linked to cancer, and specific markers of tumor aggressiveness.

Natasha Kyprianou, PhD, Navneet Dogra, PhD, and Ashutosh Tewari, MD, received a MPI R01 grant from the National Cancer Institute for “Molecular Profiling of the Tumor Microenvironment in Prostate Cancer Progression.” The project aims to define the mechanisms underlying the phenotypic profiles of the prostate tumor microenvironment that are characteristic of invasive behavior and therapeutic resistance during progression to metastasis. Findings will support development of strategies to induce prostate tumor therapeutic vulnerability and overcome lethal metastatic castration resistant prostate cancer, and novel signatures for diagnosis of lymph node invasion and tumor recurrence.

Elvin Wagenblast, PhD, and Sai Ma, PhD, were awarded R21 grant funding from the National Cancer Institute for “Characterizing DNA Methylation Dynamics in Trisomy 21-Associated Hematopoiesis and Leukemia.” This project will map DNA methylation, chromatin accessibility, and gene expression at single-cell resolution to uncover how epigenetic changes in trisomy 21 blood stem cells drive the development of Down syndrome-associated leukemia, with the goal of identifying new therapeutic targets.

Elvin Wagenblast, PhD

Sai Ma, PhD

Tingting Jiang, PhD, received R01 grant funding from the National Heart Lung and Blood Institute for “Development of a Versatile Paired Prime Editing Toolkit for CFTR Gene Correction.” This project will focus on a generalizable genome editing strategy for correction of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The goal is to develop paired prime editing-based sequence replacement strategies to correct a broad spectrum of CFTR mutations, regardless of the mutation types or locations.

Criseyda Martinez, PhD, with the Irie Laboratory, was awarded an American Cancer Society Postdoctoral Fellowship for “Targeting PTK6 in TNBC: Mechanistic Insights and Efficacy of a Novel PROTAC Degrader.” 

The Biostatistics Shared Resource Facility (BSRF) has transitioned its service request process to a new REDCap-based form to streamline access and improve usability, including availability outside the Sinai intranet. To request biostatistical support, please use the new form.

For information about the BSRF—services, funding models, policies, etc.—visit the BSRF website.  Questions can be directed to Erin Moshier, MSc, Managing Director.

A new Phase 3 clinical trial for metastatic non-small-cell lung cancer is now open: Radiotherapy to Block Oligoprogression in Metastatic Non-Small-Cell Lung Cancer (CURB2), NCT06686771. Sponsored by the Canadian Cancer Trials Group, the trial aims to determine if the chance of lung cancer growing or spreading can be lowered by adding targeted radiotherapy to the usual combination of drugs. Robert Samstein, MD, PhD, is the Mount Sinai Site PI. Patient enrollment will take place at The Mount Sinai Hospital, The Blavatnik Family Chelsea Medical Center and Mount Sinai West.

Deborah Doroshow, MD, PhD, is the Mount Sinai Site PI for A Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation, NCT06560645, an international Phase 1 trial that is halfway through dose escalation. Sponsored by Prelude Therapeutics, the study aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation. Patients with lung and GI cancers are being prioritized for the study. 

Rima Patel, MD; Erin Moshier, MS; Amy Tiersten, MD, and colleagues

Randomized Phase II Comparison of Single-agent Carboplatin Versus Combination of Carboplatin and Everolimus for Advanced Triple Negative Breast Cancer

Breast Cancer Research and Treatment. 2025 Aug 16. PMID: 40817986

This randomized phase II clinical trial in patients with metastatic triple negative breast cancer (TNBC) demonstrated that the combination of carboplatin and everolimus was associated with a statistically significant improvement in progression free survival compared to carboplatin alone with a 52 percent reduction in risk of disease progression or death. Everolimus blocks the mTOR pathway, which gets turned on and causes tumor proliferation when TNBC tumors experience loss of the PTEN gene. The combination treatment was well tolerated and there was a low incidence of discontinuation due to adverse events.

Press Release

Sacha Gnjatic, PhD, and colleagues

Multiparametric Cellular and Spatial Organization in Cancer Tissue Lesions With a Streamlined Pipeline

Nature Biomedical Engineering. 2025 Aug 25. PMID: 40855123

Dr. Gnjatic and colleagues have developed an open-source, user-guided automated pipeline that streamlines start-to-finish, single-cell resolution analysis of whole-slide tissue. The multiplex-imaging analysis, registration, quantification, and overlaying (MARQO) tool integrates elastic image registration, iterative nuclear segmentation, unsupervised clustering with mini-batch k-means and user-guided cell classification through a graphical interface. MARQO provides pathologists and researchers with a necessary tool to quantitatively analyze whole-slide imaging data, which can augment future discoveries and bolster the field of cancer immunology.

Press Release

Balagopal Pai, PhD; Susana Isabel Ramos, PhD; Raymund Yong, MD; Elena Zaslavsky, PhD; Robert Sebra, PhD; Nadejda Tsankova, MD, PhD

Spatial Multi-omics Defines a Shared Tumor Infiltrative Signature at the Resection Margin in High-Grade Gliomas

Cancer Research. 2025 Aug 4. PMID: 40759029

This study used tissue from rare supratotal neurosurgical resections of high-grade glioma/glioblastoma to generate a new multi-omic dataset that profiles tumor and tumor microenvironment populations at the infiltrative margin as well as the core—residual disease at the infiltrative margin typically predicts treatment response and drives recurrence. The dataset capture the full array of TME cell types, enabling further studies aimed at residual disease.

Christine Chen, MD; Laurie Margolies, MD, and colleagues

Breast Lymphoma: Imaging Features, Clinical Presentation, and Ultrasound Artificial Intelligence (AI) Decision Support (DS)

Clinical Imaging. 2025 Aug 12. PMID: 40803140

Dr. Margolies and team present an update on prevalence and clinical presentation of breast lymphoma (BL)—a rare hematologic neoplasm arising from breast lymphoid tissue—within a diverse population. They identify common and uncommon radiology features of primary BL and secondary BL. This study was the first analysis of artificial intelligence (AI)-based ultrasound decision support (DS) for detection of breast lymphoma; AI DS was found to be fairly accurate in flagging the majority of BL lesions as suspicious.

Rudra Prasad Dutta, PhD; Samir Parekh, MBBS, and colleagues

SOX11 Modulates BCR Signaling Through the PAX5/CD19 Axis for Therapeutic Targeting in BTK Resistant Mantle Cell Lymphoma

Blood Advances. 2025 Aug 22. PMID: 40845256

Mantle cell lymphoma is an incurable subtype of B-cell non-Hodgkin lymphoma that is treated with BTK inhibitors, and resistance to BTK inhibition is a significant clinical challenge. This paper focuses on the contribution of the transcription factor SOX11 to the regulation of the BCR signaling pathway and demonstrates that SOX11 contributes to BTK resistance in MCL via the PAX5/CD19 axis. Targeting SOX11 using SOX11 inhibitors developed at Mount Sinai overcomes BTK resistance by disrupting the BCR signaling pathway, leading to cell death in therapy-resistant MCL cells. Dr. Parekh and team also show efficacy of SOX11 small molecule inhibition in vivo in MCL xenograft models. SOX11 inhibition therefore offers significant potential for MCL patients, especially BTKi resistant patients, by targeting upstream resistance mechanisms.

Matthew Galsky, MD, and colleagues

Adjuvant Nivolumab in Muscle-invasive Urothelial Carcinoma: Exploratory Biomarker Analysis of the Randomized Phase 3 CheckMate 274 Trial

Nature Medicine. 2025 Aug 7. PMID: 40775055

To assess the relevance of key biomarkers in the setting of adjuvant muscle-invasive urothelial carcinoma, extensive exploratory analyses of tumor biomarkers, including associations with disease-free survival, were performed. Overall, the results of this analysis from the CheckMate 274 trial (NCT02632409) advance an understanding of the prognostic and predictive aspects of several tumor microenvironment and cancer cell-intrinsic features, extend their application to the adjuvant setting, and identify putative predictive biomarkers, such as TGFβ signaling and CD4, for further mechanistic exploration and clinical investigation.

Zachary Avigan, MD; Jerrel Catlett, PhD; Santiago Thibaud, MD, and colleagues

Clonal Hematopoiesis and Inflammation Predict Hematologic Toxicity and Secondary Myeloid Malignancies After BCMA-directed Chimeric Antigen Receptor T Cell Therapy

Clinical Cancer Research. 2025 Aug 13. PMID: 40801897

In this study, 213 myeloma patients treated with B-cell maturation antigen (BCMA)-directed CAR-T at Mount Sinai were analyzed to characterize clinical, inflammatory, and myeloid clonal features associated with hematologic toxicity—the study represents the largest and most detailed characterization of cytopenias following BCMA-directed CAR-T reported to date. Findings showed that the combination of clonal hematopoiesis (CH) and baseline inflammatory markers was highly associated with prolonged cytopenias compared to either risk factor alone and that progression to secondary myeloid malignancy was associated with selective expansion of pre-existing TP53-mutated myeloid clones. These findings have significant implications for risk stratification and patient selection, particularly for those with TP53 CH.

Fred R. Hirsch, MD, PhD; Triparna Sen, PhD, and colleagues

Molecular Landscape and Therapeutic Strategies of Lung Cancer Lineage Plasticity

Journal of Thoracic Oncology. 2025 Aug 2. PMID: 40751717

The histologic transition of lung adenocarcinoma to small cell lung cancer or lung squamous cell carcinoma is increasingly recognized as a mechanism of resistance to targeted therapies. This review highlights the current knowledge of the molecular drivers, transcriptional and epigenetic programs, and immune interactions underlying the transformation process, offering insights into potential therapeutic targets to mitigate resistance mechanisms.

Lilian Varricchio, PhD; John Mascarenhas, MD; Ronald Hoffman, MD, and colleagues

Thrombocytopenia in Myelofibrosis Is Characterized by Inflammatory Megakaryocytes With Reduced G6B Expression

Blood. 2025 Jul 10. PMID: 40643151

This study provides mechanistic insight into thrombocytopenia-associated myelofibrosis (MF), highlighting the critical role of the immunoreceptor G6B in the development of thrombocytopenia in MF. The identification of a patient harboring a germline loss-of-function mutation in G6B, accompanied by megakaryocyte (MK) dysplasia, MF, and thrombocytopenia, strengthens the link between G6B dysfunction and impaired thrombopoiesis. In thrombocytopenic MF patients, MKs showed reduced G6B expression, impaired maturation, and a pro-fibrotic cytokine loop involving TGF-β1 and YKL-40—hallmark of MKs primed for inflammation rather than platelet production. These findings supported the rationale for TGF-β1 blockade with AVID200 (NCT03895112), a first-in-human, open-label, multicenter Phase I/Ib trial, which demonstrated clinical benefit in thrombocytopenic MF patients resistant to ruxolitinib therapy.

Raja Flores, MD, and Brian Houseman, MD, are the authors of The VATS Lobectomy Book : A Safe and Simple Method of Performing Minimally Invasive Lobectomy for Lung Cancer.

Lina Jandorf, MA; Tatiana Ramirez, BA, and colleagues report in Health Education Research on the Community Outreach and Engagement lung cancer education and navigation program utilizing Lay Health Navigators to educate at-risk community members about lung cancer and guide them to low-dose computed tomography screening. Evaluation of the program shows that quality training materials can successfully prepare volunteers who share language and culture with the at-risk communities to provide these navigation services.

Lay health navigators: an initiative to navigate community members into lung cancer screening

Health Education Research, 2025 Aug 12. PMID: 40891907

In other Community Outreach and Engagement (COE) news, TCI Community Scientist Colette Smith led “HEALing the Bronx,” a community event on August 23, with support from COE. “HEALing the Bronx” is a grassroots effort focused on increasing health awareness and education. Melissa Mazor, PhD, MS, RN; Sarah Miller, PsyD, and TCI Community Scientist Jean Claude Noel attended the event.

Instagram Reel

This summer, The Tisch Cancer Institute hosted three medical students with the Robert A. Winn Clinical Investigator Pathway Program. The six-week program immerses medical students in community-based clinical research; they presented their work at a culminating event at NYU.

• Bishoy Yacoub and Storm Alexander – Predictors of Second Lung Cancer Resection: A Cohort Study of 1600 Patients. Mentored by Stephanie Tuminello, PhD, MPH, and Emanuela Taioli, MD, PhD

• Melissa Castillo – Intravoxel Incoherent Motion in Female Pelvic Tissue. Mentored by Deborah Marshall, MD

September 16

Giorgio Inghirami, MD, Weill Cornell Medical College

“Assessing Therapeutic Avenues to Overcome the Refractorness of Diffuse Large B-clls Lymphoma Using Fully Humanized Mice Models”

Hosted by Amir Horowitz, PhD

September 23

Betty Kim, MD, PhD, MD Anderson Cancer Center/Baylor College of Medicine

“Messages in a Vesicle: mRNA Therapy for Cancer and Other Human Diseases”

Hosted by Yizhou Dong, PhD

September 30

XingXing Zang, PhD, Albert Einstein College of Medicine

“New Immune Checkpoings: From Fundamental Biology to Novel Drugs to New Clinical Trials”

Hosted by Lucas Ferrari de Andrade, PhD

Precision Immunology Institute Seminar Series

Tuesday, September 16, 2 pm, Davis Auditorium



Kathleen H. Burns, MD, PhD, Chair, Department of Pathology, Dana-Farber Cancer Institute

“A Retrotransposon in Cancer: The Marker and the Mutator”

The multiple myeloma team is presenting numerous abstracts at the 2025 Annual Meeting of the International Myeloma Society (September 17-20 in Toronto), including four recognized with the IMS Young Investigator Award for Exemplary Abstract:

• Tarek Mouhieddine, MD: “Baseline and Longitudinal Immune and Inflammatory Correlates of Response to Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma”

• Adolfo Aleman, PhD: “TET2 and EZH2 Genetic Alterations Promote Malignant CAR-T Transformation in anti-NCMA CAR-T Therapy”

• Oliver Van Oekelen, MD, PhD: “S100A8/A9 Promotes T Cell Exhaustion and Impairs Response to Bispecific Therapy in Multiple Myeloma”

• Abigail Chutnik, MD: “Delayed Hematologic Recovery After BCMA CAR-T Is Associated With Progressive Loss of Endogenous T Cell Diversity After CAR-T Infusion” 

Emily Bernstein, PhD, will be a Keynote Speaker at the 5th Translational Genomics & Epigenomics Symposium, September 18-19, at Roswell Park Comprehensive Cancer Center in Buffalo. Her talk is titled “Mechanisms of Chromatin Remodeling Mutations in Cancer.”

Emanuela Taioli, MD, PhD, is presenting “Update on global Epidemiology of Mesothelioma and Asbestos” at iMig 2025 | 17th International Conference of the International Mesothelioma Interest Group, October 26-29, in Philadelphia.

Joseph Sparano, MD, is giving two presentations at the 23rd Annual School of Breast Oncology, taking place November 6-8 in Atlanta.

• “Considerations in Systemic Therapy for Early-Stage Triple Negative Breast Cancer”
• “The Art and Science of Managing HER2-Negative Metastatic Breast Cancer”

Use code SOBOSAP for free registration.

Fred R. Hirsch, MD, PhD, had an oral presentation at the 2025 IASLC World Conference on Lung Cancer in Barcelona, September 5-9: “Molecular Characteristics of NSCLC and Prognosis.”

Deborah Doroshow, MD, PhD, was co-author on a poster presented at the IASLC conference: “Long-Term Overall Survival in Advanced EGFRm NSCLC Treated With 1L Osimertinib: Results From the US, Japan, Germany and China.”

The Chemotherapy Foundation Symposium will be held November 12-14 at the New York Hilton Midtown. John Mascarenhas, MD, is Program Co-Chair.



Information and Registration (Use code MASCARENHAS for free registration)