September 2023

Shrabanti Chowdhury, PhD; Pei Wang, PhD; and colleagues



Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

Cell. 2023 Aug 3. PMID: 37541199

High-grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, has a five-year survival rate of 30 percent. Ten to 20 percent of HGSOC patients have treatment-refractory disease. Because there is no way to distinguish refractory from sensitive HGSOCs prior to therapy, patients with refractory disease experience the toxicity of platinum-based chemotherapy without benefit. Drs. Chowdhury and Wang and colleagues characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs and identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy. They also identified five molecular subtypes. Once validated via additional studies, the findings may inform customized alternative treatments.

Press Release

Dmitriy Zamarin, MD, PhD, has joined Mount Sinai as Associate Professor of Medicine (Hematology and Medical Oncology) and Head of the Section of Gynecologic Medical Oncology. He sees patients at The Blavatnik Family Chelsea Medical Center. Dr. Zamarin is a physician scientist with a clinical and laboratory research focus on immunotherapy for gynecologic cancers. Dr. Zamarin earned his MD and a PhD in Virology from the Icahn School of Medicine at Mount Sinai. He completed residency in Internal Medicine at The Mount Sinai Hospital and fellowship in Hematology and Medical Oncology at Memorial Sloan Kettering Cancer Center (MSK). Dr. Zamarin was most recently on the faculty at MSK, where he served as Translational Research Director in Gynecologic Medical Oncology and was actively involved in early drug development. Dr. Zamarin has served as a principal investigator on a number of investigator-, industry-, and cooperative group-sponsored clinical trials and is the translational chair of the NRG Oncology cervical cancer committee. He has published numerous articles and received extensive research funding from government, foundation, industry, and philanthropic entities, including recent R01 grants from the National Cancer Institute: “Potentiation of Anti-Tumor Immunity by Oncolytic Virus in Situ Vaccination” and “Immunogenomic Predictors of Outcomes in Patients With Locally Advanced Cervical Cancer Treated with Immunotherapy and Chemoradiation.”

CV

Dan Feng, MD, PhD, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology). Her clinical practice focus is on hepatobiliary and gastrointestinal cancers; she sees patients at The Mount Sinai Hospital. Additionally, Dr. Feng will collaborate with the Precision Immunology Institute on translational research involving tissue specimen analysis. Dr. Feng earned her PhD in Cell and Molecular Biology from the University of Pennsylvania and her MD from Stanford University School of Medicine. She completed residency in Internal Medicine at New York Presbyterian Hospital/Weill Cornell Medical Center and fellowship in Medical Oncology at Memorial Sloan Kettering Cancer Center, where she also did postdoctoral research on colorectal cancer and immunotherapy.

Borna Mohabbatizadeh, MD, MS, has joined Mount Sinai as Assistant Professor of Surgery, Division of Breast Surgery. He sees patients at the Dubin Breast Center and Mount Sinai West Breast Surgery Center. Dr. Mohabbatizadeh completed a Breast Surgical Oncology fellowship at Mount Sinai West and The Blavatnik Family Chelsea Medical Center. He did residency training in General Surgery at Kaiser Permanente Los Angeles Medical Center and earned his MD from Virginia Commonwealth University. Dr. Mohabbatizadeh also has a Master of Science degree in Human Nutrition from Columbia University.

Hannah Levavi, MD, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology) with a clinical focus on leukemia. She sees patients at The Mount Sinai Hospital. Dr. Levavi completed residency in Internal Medicine and fellowship in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai. She served as both Chief Resident and Chief Fellow. Dr. Levavi earned her MD at the Warren Alpert Medical School of Brown University. Her research focuses on acute lymphoblastic leukemia (ALL), with recent research projects investigating methotrexate neurotoxicity in adults with ALL, TP53 alterations in ALL, and CGH+SNP array in ALL.

Miriam Merad, MD, PhD, and Brian Brown, PhD, are leading the newly-established Department of Immunology and Immunotherapy (DII) at the Icahn School of Medicine at Mount Sinai. In collaboration with The Tisch Cancer Institute, the Icahn Genomics Institute, and the Marc and Jennifer Lipschultz Precision Immunology Institute, the DII will facilitate cutting-edge gene and cell engineering technologies that enable scientific inquiries about the immune system and development of innovative immunotherapies.

Nina Bhardwaj, MD, PhD, and Miriam Merad, MD, PhD, will be inducted into the Society for Immunotherapy of Cancer’s (SITC’s) 2023 Class of Fellows of the Academy of Immuno-Oncology. Dr. Bhadwaj and Dr. Merad were chosen for their longstanding dedication to the field of cancer immunotherapy. The induction ceremony will take place on November 3 at SITC’s 38th Annual Meeting in San Diego.

Gagan Sahni, MD, Director of Cardio-Oncology, has joined the Board of Directors of Livestrong. Dr. Sahni has established an award-winning cardio-oncology program at Mount Sinai and has expertise in treating heart disease in cancer patients and survivors. Additionally, Dr. Sahni has developed institution-wide protocols for early detection and monitoring of cardiotoxicity due to cancer treatments, including chemotherapy, radiation therapy and immunotherapy.

Triparna Sen, PhD, was invited to serve as a member of the Career Development and Fellowship Committee of the International Association for the Study of Lung Cancer (IASLC). Deborah Doroshow, MD, PhD, is also a committee member. Additionally, Dr. Sen is serving on the Programming/Organizing Committee for the IASLC 2023 North American Conference on Lung Cancer, to be held December 1-3.

Daniel Puleston, PhD, received a National Institutes of Health DP2 New Innovator Award for “Exploring Metabolic Governance of Immune Cell Form and Function”. The goal of the project is to develop new ways to explore in situ cellular metabolism of immune cells in mice and humans and identify novel metabolic pathways essential for immunity.

Igor Bado, PhD, received a 2023 Breast Cancer Research Foundation –AACR Nextgen Grant for Transformative Cancer Research. He will investigate the role of FGF2 in determining the fate of disseminated breast cancer cells in the bone. Ultimately, this project will enhance understanding of mechanisms contributing to cancer cell survival in the bone microenvironment.

Maaike van Gerwen, MD, PhD, received a U01 grant award from the National Institute for Occupational Safety and Health for “The Effect of WTC Exposure on Thyroid Cancer in the Survivor Population.” This project will focus on the potential impact of (early life) exposure to the World Trade Center (WTC) dust cloud on thyroid carcinogenesis and cancer aggressiveness. It will be the first in-depth study to investigate thyroid cancer in the WTC survivor population, including an assessment of thyroid cancer in patients exposed as children or adolescents. Identifying phenotypes and biomarkers associated with increased risk of more aggressive thyroid cancer will help identify patients needing more aggressive screening and management.

Alan Shih, MD, PhD, has been awarded a grant from the Leukemia Research Foundation for “Screening and Validating New Targets in Acute Leukemias.” Azacytidine and venetoclax combination is a standard of care for many patients with AML; azacytidine targets DNA methylation and venetoclax targets a pathway that allows leukemia cells to survive. Dr. Shih’s project will seek to augment this combination therapy by identifying new epigenetic-dependency genes, leading to new targets and drugs and novel approaches that activate cell death pathways.

Poulikos Poulikakos, PhD, received a 2023 Translational Award from the V Foundation for “Rational Combination Strategies to Overcome Therapeutic Resistance to RAS Pathway Inhibitors.” With co-investigators Rajwanth Veluswamy, MD, and Pei Wang, PhD, Dr. Poulikakos will pursue the rational development of more effective and safer drugs and drug combinations targeting RAS-mutant cancers.

Igor Bado, PhD, and Amir Horowitz, PhD, are the new directors of the TCI Seminar Series, taking over from Jerry Edward Chipuk, PhD, and Amaia Lujambio, PhD. The series takes place on Tuesdays at 12 pm and features a range of topics such as immunology, metastasis, metabolism, epigenetics, and cancer evolution. TCI members are encouraged to suggest speakers—please contact Theresa Choi, Seminar Coordinator, Dr. Bado or Dr. Horowitz for assistance with scheduling and invitations.

Upcoming Seminars

September 12, 12 pm, Davis Auditorium

"Everything You Wanted to Know About Entrepreneurship and Commercialization in Cancer"

Q&A with Erik Lium, PhD, Chief Commercial innovation Officer and President, Mount Sinai Innovation Partners

Hosted by Ramon Parsons, MD, PhD, and Scott Friedman, MD

September 19, 12 pm

Dieter Henrik Heiland, MD, PhD

Department of Neurosurgery, Medical Center University of Freiburg

Department of Neurological Surgery, Northwestern University

"Temporal Topography of Malignant Brain Tumors"

Hosted by Dolores Hambardzumyan, PhD, MBA

Etienne Humblin, PhD; Dan Filipescu, PhD; Alice Kamphorst PhD; and colleagues

Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1⁺ PD-1⁺ CD8 T cells

Science Immunology. 2023 Aug 25. PMID: 37624910

Immunotherapies targeting the PD-1 pathway have changed the landscape of cancer treatment. TCF-1⁺ PD-1⁺ CD8 T cells (precursors to exhausted cells, Tpex) respond to PD-1 blockade by differentiating into cells with anti-tumor activity. Tpex have high expression of CD28, and CD28 costimulation is required for reinvigoration of CD8 T cells during PD-1 targeted therapies.

Dr. Kamphorst et al. set out to understand the role of CD28 for PD-1⁺ CD8 T cells. They found a central role of CD28 in preserving metabolic fitness; sustained CD28 costimulation was required to maintain PD-1⁺ CD8 T cell responses and higher levels of CD28 costimulation promoted Tpex differentiation. Importantly, the data suggest that engaging the CD28 pathway may improve T cell function without compromising longevity of responses.

Julia Blanter, MD; Julie Fasano, MD; Paula Klein, MD; Theresa Shao, MD; Aarti Bhardwaj, MD; Amy Tiersten, MD; and colleagues

Results of a phase Ib study investigating durvalumab in combination with eribulin in patients with HER2-negative metastatic breast cancer and recurrent ovarian cancer

Oncology. 2023 Aug 18. PMID: 37598677

This study sought to determine the maximum tolerated dose and recommended phase II dose of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative metastatic breast cancer (MBC) and recurrent ovarian cancer. The combination had a favorable adverse event profile. The early anti-tumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.

https://clinicaltrials.gov/study/NCT03430518

Jonathan Anker, MD, PhD; Nina Bhardwaj, MD, PhD; Sacha Gnjatic, PhD; Matthew Galsky, MD; and colleagues

Antitumor immunity as the basis for durable disease-free treatment-free survival in patients with metastatic urothelial cancer

Journal for Immunotherapy of Cancer. 2023 Aug. PMID: 37607770

This study sought to identify the genomic and immunological mechanisms associated with functional cure of patients enrolled in a phase II trial evaluating a phased schedule of gemcitabine and cisplatin followed by gemcitabine and cisplatin with ipilimumab for metastatic urothelial cancer. Findings suggest that a pre-existing adaptive immune response, enhanced by treatment with cisplatin-based chemotherapy and ipilimumab, may be responsible for long-term remission. Neoantigen-specific T cells may play a critical role in this response. The identification of markers of response may help identify patients most likely to benefit from chemotherapy plus immune checkpoint inhibitor-based therapy.

Emily Bernstein, PhD; Dan Filipescu, PhD; Dan Hasson, PhD; Miriam Merad, MD, PhD; Alice Kamphorst, PhD; Robert Sebra, PhD; Helene Salmon, PhD; and colleagues



MacroH2A restricts inflammatory gene expression in melanoma cancer-associated fibroblasts by coordinating chromatin looping

Nature Cell Biology. 2023 Aug 21. PMID: 37605008

Histone variant dysfunction has profound consequences for tumor cells; however, their role in the tumor microenvironment (TME) remains unclear. Using a preclinical melanoma model, Dr. Bernstein and team demonstrate that mice lacking macroH2A develop larger tumors, accompanied by accumulation of immunosuppressive monocytes and depletion of functional cytotoxic T cells. This compromised anti-tumor response stems from increased inflammatory gene expression in cancer-associated fibroblasts, where macroH2A deficiency promotes 3D chromatin interactions between inflammatory genes and active enhancer elements. This unique role for macroH2A in the TME is conserved in human melanoma with implications for the clinical management of this highly aggressive malignancy.

Scott Roof, MD; Rocco Ferrandino, MD; Sida Chen, MD; Krzysztof Misiukiewicz, MD; Marshall Posner, MD; Eric Genden, MD; Raymond Chai, MD; and colleagues

Negative predictive value of circulating tumor tissue modified viral (TTMV)-HPV DNA for HPV-driven oropharyngeal cancer surveillance

Clinical Cancer Research. 2023 Aug 11. PMID: 37566241

Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Findings from this retrospective observational cohort study of 543 patients support the clinical utility of TTMV-HPV DNA as a circulating tumor-derived biomarker to monitor HPV-driven OPSCC survivors for recurrence during post-treatment surveillance. The data could inform decisions on when to pursue re-imaging following first disease restaging and future surveillance practice. 

Alex Rialdi, MPH; Mary Duffy, PhD; Augusto Villanueva, MD, PhD; Dan Hasson, PhD; Josep Llovet, MD, PhD; Amaia Lujambio, PhD; Ernesto Guccione, PhD; Arvin Dar, PhD; and colleagues

WNTinib is a multi-kinase inhibitor with specificity against β-catenin mutant hepatocellular carcinoma

Nature Cancer. 2023 Aug 3. PMID: 37537299



This study identifies WNTinib as a multi-targeted kinase inhibitor (KI) with selective efficacy in β-Catenin (CTNNB1)-mutated hepatocellular carcinoma (HCC), which makes up 30% of cases of HCC with no precision therapeutics available. Multiomic and target engagement analyses revealed that WNTinib is superior to clinical KIs and inhibits KIT/mitogen-activated protein kinase signaling at multiple nodes. The study provides the rationale to explore WNTinib in proof-of-concept trials with patients with enriched CTNNB1-mutant advanced HCC.

Sarah Cappuyns, MD, PhD; Virginia Corbett, MD; Josep Llovet, MD, PhD; and colleagues

Critical appraisal of guideline recommendations on systemic therapies for advanced hepatocellular carcinoma: a review

JAMA Oncology. 2023 Aug 3. PMID: 37535375

This review found that the combination of atezolizumab, an immune checkpoint inhibitor, plus bevacizumab, an antiangiogenic agent, is considered the primary standard of care for advanced hepatocellular carcinoma (HCC) in the first-line setting, whereas durvalumab plus tremelimumab is also acceptable. The findings, from integrating the recommendations from scientific societies’ guidelines for managing advanced HCC along with new data from cross-trial comparisons, may aid clinicians in decision-making and guide them through a rapidly evolving and complex treatment landscape.

Vinayak Wagaskar, MD; Osama Zaaytoun, MD; Swati Bhardwaj, MD; Ash Tewari, MD

'Stealth' prostate tumors

Cancers (Basel). 2023 Jul 4. PMID: 37444597

The aim of this retrospective study of 3600 prostate cancer (PCa) patients was to determine the false negative rates of prebiopsy MRI and MRI-ultrasound 12-core systematic prostate biopsy by analyzing radical prostatectomy specimens. Findings showed significant rates of false negatives in the standard diagnostics of PCa, supporting the need for further strategies to improve the accuracy of diagnosis and identification of tumor location.

TCI hosted a scholar in the Medical Student Training in Aging Research (MSTAR) Program during the summer. This T32 funded program, supported by the National Institute of Aging, provides medical students with a 12-week immersive exploration of research methodologies, platforms for research presentations and opportunities for publications, and clinical geriatrics and palliative medicine exposure. Sach Thakker, medical student at Georgetown University School of Medicine, joined the laboratory of Jerry Edward Chipuk, PhD, to explore how mitochondrial stress signaling impacts melanoma. Sach also received clinical mentorship from Nicholas Gulati, MD, PhD (Dermatology), and will present a poster at the 20th International Congress of the Society for Melanoma Research, to be held November 6-9 in Philadelphia.

Philip Mack, PhD, will present at the NCI Cancer Diagnosis Program Workshop: ctDNA in Cancer Treatment and Clinical Care, September 14-15, at the NCI Shady Grove campus (also via livestream). Dr. Mack’s presentation: "ctDNA Kinetics Predicts PFS and OS in EGFR TKI-treated Patients with EGFR-Mutant NSCLC."

Christian Rolfo, MD, PhD, and Triparna Sen, PhD, are invited speakers at the International Lung Cancer Survivorship Conference, September 22-23. The virtual educational conference will provide information for patients with lung cancer and caregivers.

• Dr. Rolfo—"Liquid Biopsy: Current Capabilities and Future Potential"
• Dr. Sen—"Histological Transformation of NSCLC into SCLC"

Dr. Sen has also been invited to be a panelist at the Binaytara Foundation’s 2023 Annual Symposium for Evolving Therapies and Drug Development in Oncology, a conference for oncology providers, September 29-30. Dr. Sen will participate in the Future of Drug Development in Oncology session.

Poulikos I. Poulikakos, PhD, will co-chair a workshop, Exploring Combination Therapies that Assist RAS-Targeted Drugs in Ensuring Cancer-Free Survival, at the 5th Annual RAS-Targeted Drug Development Summit, September 26-28, in Boston. 

Sundar Jagannath, MD; Samir Parekh, MD; and Joshua Richter, MD, will present at the International Myeloma Society Annual Meeting,

September 27-30, in Athens.

• Dr. Parekh—"Single Cell Genomic Techniques for Study of Myeloma"
• Dr. Richter—"Prevention and Monitoring of Infections with Immunotherapies"
• Dr. Jagannath—Round Table Discussion: Challenges in Multiple Myeloma

Jennifer Marti, MD, breast surgeon at Mount Sinai-Union Square, presented “Active Surveillance of DCIS” at the 5th Annual Breast Cancer Symposium: Disparities on a Cellular Level & Patient Level, held August 4-6. Dr. Marti will also present at the 2024 symposium. The symposia are produced by New York Oncology Hematology in collaboration with the American Cancer Society.

TCI Community Outreach and Engagement Retreat

September 29, 10 am - 1:30 pm

Annenberg Building, 5-205 (also via Zoom)

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Registration

Cardinale Smith, MD, PhD, is chairing the ASCO Quality Care Symposium, October 27-28. The meeting—in person in Boston and online—addresses quality, safety, and efficiency of cancer care. Registration

John Mascarenhas, MD, is co-chairing The Chemotherapy Foundation Symposium, November 8-10 in New York City. Use “Mascarenhas” for free registration. 

A Service of Remembrance, honoring and celebrating cancer patients, will be held on October 18 at 12 pm and October 26 at 6 pm.

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