January 2025

Josep Llovet, MD, PhD, and colleagues

Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study 

Lancet. 2025 Jan 9. PMID: 39798578

This study, coordinated by Josep M Llovet, MD, PhD, Director of the Mount Sinai Liver Cancer Program, evaluated the addition of lenvatinib and pembrolizumab to transarterial chemoembolization (TACE) for patients with intermediate-stage, unresectable non-metastatic hepatocellular carcinoma. Ever since TACE was established as standard of care 20 years ago, previous attempts to combine it with systemic therapies have failed to deliver clinical benefit. This is the first study to show a statistically significant improvement in progression-free survival using a combination of a tyrosine kinase inhibitor, immunotherapy, and TACE. It addresses an unmet need in this patient population, and the new therapy will be proposed as the new standard of care in the coming Clinical Practice Guidelines. 

Press Release

Jerry Edward Chipuk, PhD, was recently appointed as a Full Member of the American Society for Cell Biology LGBTQ+ Committee for a three-year term. The committee focuses on the importance of diversity and inclusion in fostering innovation and collaboration.

Joshua Brody, MD; Keith Sigel, MD, PhD; and Dmitriy Zamarin, MD, PhD, have been elected as new members of The American Society for Clinical Investigation (ASCI). They will be inducted into the Society on April 25.

The ASCI is a medical honor society dedicated to the advancement of research that extends understanding of diseases and improves treatment, and mentorship of future generations of physician-scientists.

Nadejda Tsankova, MD, PhD, was awarded a five-year R01 grant from the National Institute of Neurological Disorders and Stroke to support her work on anti-invasive therapeutics in glioblastoma tumors. The project, “Harnessing YAP-TEAD Activity as Anti-Invasion Therapeutic in Human Glioblastoma,” is a continuation of her previous R01-funded research investigating the Hippo pathway but with a more translational focus. It advances prior efforts to define glioblastoma migration drivers, towards a clinically relevant goal of repurposing YAP-TEAD inhibitors as anti-invasion therapeutics, by screening for drugs with optimal oral bioavailability and preclinical efficacy and defining rational biomarkers of response across primary and recurrent tumor subtypes. Dr. Tsankova’s research is conducted in collaboration with Raymund Yong, MD (Neurosurgery), Elena Zaslavsky, PhD (Neurology) and Dolores Hambardzumyan, PhD, MBA (Oncological Sciences).

Zhe Ying, PhD, was awarded grant funding from the American Association for Cancer Research—Triple Negative Breast Cancer Foundation-AACR NextGen Grant for Transformative Cancer Research—for “Branching Out: How do Basal-like Breast Cancer Driver Mutations Initiate Hormone Independence?” Dr. Xing’s research focuses on understanding how key driver lesions of triple-negative breast cancer hijack the fundamental mechanisms of mammary gland development, with the goal of advancing molecular targeted therapies.

Camillia Azimi, PhD, a member of the Merad Lab and Brown Lab, was named a 2024 Hanna Gray Fellow by the Howard Hughes Medical Institute. Dr. Azimi’s research focuses on engineering novel chimeric antigen receptors to reprogram macrophages at the disease site for targeted control of the disease. Her work seeks to expand understanding of macrophage signaling and to modulate macrophage behavior with an aim to develop new approaches in innate immunotherapy.

Awardees are selected for their demonstrated commitment to making foundation discoveries while building an inclusive culture in academic science.

2024 TCI Developmental Fund Awardees were announced in December:

• Cathie Pfleger, PhD (Cancer Mechanisms) and Julie Schnur, PhD (Cancer Prevention and Control): "Drosophila Models of Aromatase Inhibitor-induced Musculoskeletal Pain (AI-MSP)"
• Jose Javier Bravo-Cordero, PhD (Cancer Mechanisms) and Lucas Ferrari de Andrade, PhD (Cancer Immunology): "Regulation of Breast Cancer Metastatic Dormancy by Sensory Neurons and NK Cells"
• David Mulholland, PhD (Cancer Mechanisms) and John Sfakianos, MD (Cancer Clinical Investigation): "Sensitizing Bladder Cancer to Enfortumab Vedotin (EV) by Targeting WNTb-Catenin Signaling"

The TCI Developmental Fund Awards support translational and/or epidemiological projects that are intra- and inter-collaborations between TCI members.

Shared Resources Annual Survey

TCI members and laboratory staff, including students, are encouraged to complete the TCI Shared Resources Annual Survey. Responses to the survey will inform how TCI Shared Resources are meeting research needs and identify opportunities for improvement.

Questions can be addressed to Jerry Edward Chipuk, PhD, Associate Director, Shared Resources at TCI. 

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.

Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data

Nature Medicine. 2025 Jan 6. PMID: 39762425

Dr. Chowell and team developed a machine learning system, called SCORPIO, to predict whether patients across diverse cancer types will benefit from immune checkpoint inhibitors (ICIs) without having to use advanced genomic or immunologic assays. In external cohorts, SCORPIO, which relies on routine blood tests and basic clinical data, maintained robust performance in predicting ICI outcomes. It can help prioritize treatment options between ICI, cytotoxic and targeted therapies, assess the risk-benefit ratio of ICI for patients at risk of immune-related adverse events, and guide clinical trial design by selecting or enriching patients more or less likely to benefit from ICIs.

Press Release

Rudra Dutta, PhD; Santiago Thibaud, MD; Alessandro Lagana, PhD, and colleagues

Predictors of response to venetoclax and therapeutic potential of CDK7 inhibition in multiple myeloma

Blood Neoplasia. 2024 Nov 23.

This study is the first to look at genetic markers in patients with multiple myeloma (MM) who are receiving venetoclax, a B cell lymphoma 2 (BCL-2) inhibitor. Using RNA-seq analysis, Dr. Lagana and team identified a six-gene signature that stratifies patients with MM by their predicted response to venetoclax. They also identified a novel approach to overcoming resistance to venetoclax through CD7 inhibition. Findings highlight the potential for personalized therapeutic strategies in MM, offering valuable insights to enhance venetoclax treatment response and overcome resistance.

Press Release

Subhamoy Chakraborty, PhD; Utsav Sen, PhD; Triparna Sen, PhD, and colleagues



Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer

Cell Reports Medicine. 2024 Dec 17. PMID: 39657664

This study demonstrates that treatment with lurbinectedin—a second-line treatment for small-cell lung cancer (SCLC)—activates the STING pathway and augments the anti-tumor immune response of PD-L1 blockade with significant tumor regression. The study provides mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and shows that the combination of lurbinectedin and PD-L1 blockade is clinically valuable in overcoming primary and adaptive resistance to immune checkpoint blockade in SCLC.

Press Release

Sacha Gnjatic, PhD; Jeremiah Faith, PhD; Jean-Frederic Colombel, MD, and colleagues

Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis

Journal of Experimental Medicine. 2025 Jan 6. PMID: 39666007

Immunotherapy-related colitis (irC) is a common immune-related adverse event during immune checkpoint inhibitor therapy for cancer. This longitudinal study demonstrates the microbiome’s instrumental nature in irC, including a clear trajectory of microbiome changes before, during, and after irC development. Findings underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.

Jian Jin, PhD; Ramon Parsons, MD, PhD, and colleagues

Harnessing the TAF1 Acetyltransferase for Targeted Acetylation of the Tumor Suppressor p53

Advanced Science. 2024 Dec 24. PMID: 39716936

A research team led by Dr. Jin, Dr. Parsons, and Wei Gu, PhD (Columbia University) demonstrated for the first time that the acetyltransferase TAF-1 can be harnessed for development of Acetylation Targeting Chimera (AceTAC), a new technology for inducing targeted protein acetylation. The team developed MS172, the first TAF-1-recruiting AceTAC of the p53 Y220C mutant, one of the most common p53 hotspot mutants. MS172 effectively acetylated p53Y220C and suppressed proliferation and clonogenicity of cancer cells harboring the p53Y220C mutation with little toxicity in normal cells. This work expands the very limited repertoire of the acetyltransferases that can be leveraged for developing AceTACs and advances the targeted protein acetylation field.

Alessia Baccarini, PhD; Brian Brown, PhD, and colleagues

Ovarian cancer-derived IL-4 promotes immunotherapy resistance

Cell. 2024 Dec 26. PMID: 39481380

To identify regulators of ovarian cancer immunity, this study employed a spatial functional genomics screen (Perturb-map), focused on receptor/ligands hypothesized to be involved in tumor-macrophage communication. Findings show heterogeneous tumor microenvironments can emerge from localized altered expression of cancer-derived cytokines/chemokines that establish immune-rich and immune-excluded neighborhoods, which drive clone selection and immunotherapy resistance. Findings also demonstrate the potential of targeting IL-4 signaling to enhance ovarian cancer response to immunotherapy.

Martina Barcena-Varela, PhD; Amaia Lujambio, PhD, and colleague

Precision models in hepatocellular carcinoma

Nature Reviews Gastroenterology and Hepatology. 2024 Dec 11. PMID: 39663463

This review describes the most innovative model systems that can be harnessed to identify precision and/or personalized therapies for hepatocellular carcinoma (HCC). It provides examples of how different models have been used to nominate candidate biomarkers, their limitations, and strategies to optimize such models. The review also focuses on understanding how well different preclinical models of HCC recapitulate the distinct factors that contribute to inter-patient heterogeneity, which in turn can influence response to therapy. 

Triparna Sen, PhD; Yosuke Dotsu, MD, PhD; Virginia Corbett, MD; Utsav Sen, PhD; Philip Mack, PhD; Fred R. Hirsch, MD, PhD, and colleagues

Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies

The Lancet Oncology. 2025 Jan. PMID: 39756451



This review explores the epidemiology, diagnosis, and staging of lung neuroendocrine neoplasms to date, and the evolving molecular landscape and biomarkers. The authors outline the various clinical outcomes, therapeutic challenges, diagnosis and management strategies, ongoing clinical trials, and future directions.

Sacha Gnjatic, PhD, and colleagues

The Society for Immunotherapy of Cancer Perspective on Tissue-Based Technologies for Immuno-Oncology Biomarker Discovery and Application

Clinical Cancer Research. 2024 Dec 3. PMID: 39625818

The Society for Immunotherapy of Cancer Biomarkers Committee summarizes important advances in biomarker technologies that support reliable classification of patient response, resistance and toxicity related to immuno-oncology care. The main technologies covered are advances in multiplex tissue staining, including proteomic profiling and transcriptomics techniques. Subsections provide a historic overview highlighting principles and details of techniques, their key metrics and ease of interpretation, limitations and recent technical improvements, and dependencies or adaptabilities for coupling to other technologies. The report highlights ongoing or completed trials utilizing the technologies and demonstrates how some provide seminal immune-oncology biomarker discoveries that may soon influence routine therapeutic regimens.

Poster award winners from the TCI Scientific Retreat, held December 6, are, from left to right (with Dr. Ramon Parsons, center), Anthony Lozano, PhD; Ana Orive-Ramos, PhD; Ashley Reid Cahn (PhD student); Matthew Brown (PhD student)

Winners not pictured: Ruben Fernandez-Rodriguez, PhD; Swarnima Singh, PhD

Winning Posters:

• Anthony Lozano, PhD (Amaia Lujambio, PhD, mentor): "MASH Selects Against Immunogenic Hepatocellular Carcinoma." Poster #34

• Ana Orive-Ramos, PhD (Poulikos Poulikakos, PhD, mentor): "Exploiting Conformation Selectivity of MAPK Inhibitors to Design RAS-mutant Selective Therapy." Poster #05

• Ashley Reid Cahn (Nicolas Vabret, PhD, and Nina Bhardwaj, MD, PhD, mentors): "Epigenetic Therapy Boosts mRNA LNP Cancer Vaccine Efficacy Through Viral Mimicry Signaling." Poster #36

• Matthew Brown (Nina Bhardwaj, MD, PhD, mentor): "Identifying Targets of Precancerous Neoantigen-specific T Cell Surveillance in Patients With Lynch Syndrome and Immune Suppression Programs Supporting Colorectal Cancer Progression." Poster #31

• Ruben Fernandez-Rodriguez, PhD (Mihaela Skobe, PhD, mentor: "Vascular Endothelial Growth Factor-C (VEGF-C) Enhances Anti-tumor Effects of Oncolytic Viral Therapy Leading to Tumor Eradication and Long-term Survival in Mouse Melanoma." Poster #11

• Swarnima Singh, PhD (Igor Bado, PhD, mentor): "Multi-faceted Role of CD83+ Macrophages in Promoting Multi-organ Metastasis in Breast." Poster #27

Poster abstracts can be found in the Scientific Retreat Program.

Yiyang Chen, MS, a member of the Chipuk Lab, successfully defended his PhD in the Cancer Biology multidisciplinary training area at the Graduate School of Biomedical Sciences. His degree will be conferred on January 30.

The goal of Yiyang’s project, “Targeting the BAX Actuating Funnel Potentiates membrane Permeabilization and Apoptosis,” is to determine how a mitochondria-produced lipid aldehyde interacts with BAX and impacts its activation. Efforts have led to the discovery of a previously understudied regulatory region of BAX, as well as the development of the first-in-class practical small molecule that targets this site, significantly potentiating BAX activation and promoting apoptosis. Yiyang is mentored by Jerry Edward Chipuk, PhD.

TCI Seminar Series

January 14

Vito Rebecca, PhD, Biochemistry and Molecular Biology, Johns Hopkins University

“Dissecting Drivers of Therapy Resistance and Metastasis in Acral Melanoma”

Hosted by Jose Javier Bravo-Cordero, PhD

January 28

Jeongwu Lee, PhD, Center for Cancer Stem Cell Research, Cleveland Clinic

“Therapy-induced Senescence and its Targeting in Brain Tumors”

Hosted by Dolores Hambardzumyan, PhD, MBA

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