August 2022

Dolores Hambardzumyan, PhD, MBA, and Oren Becher, MD, have been awarded R01 funding from the National Cancer Institute to investigate the role of myeloid cells in high-grade glioma in children. Dr. Hambardzumyan also received a NIH Exploratory/Developmental Research Grant (R21) to study immunotherapy resistance in pediatric high-grade glioma. Dr. Hambardzumyan and Dr. Becher hypothesize that myeloid cells, which comprise up to 30 percent of the cells in high-grade gliomas, are important in tumor promotion and resistance to therapy, including immunotherapy. In addition, Dr. Becher and Praveen Raju, MD, PhD, were granted funding from ChadTough – Defeat DIPG Foundation to optimize the use of an innovative drug delivery technology that crosses the blood-brain barrier to deliver the drug to the tumor site—a technology they developed—to improve patient outcomes for patients with DIPG (diffuse intrinsic pontine glioma, a brain tumor localized in a part of the brain stem called the pons).

These grant awards complement the establishment of the Mount Sinai Children’s Brain and Spinal Tumor Center at Mount Sinai Kravis Children’s Hospital.

Read More

Fred R. Hirsch, MD, PhD, and Kwok-Kin Wong, MD, PhD, are Co-Principal Investigators and Benjamin Hopkins, PhD, is Project Manager on a grant award from Stand Up To Cancer (SU2C) to investigate therapeutic options for lung cancer characterized by KRAS mutations. Most patients with non-small cell lung cancers (NSCLCs) with KRAS mutations do not respond to current therapies or develop early resistance. The partnering researchers from Mount Sinai and NYU Langone’s Perlmutter Cancer Center will aim to identify therapeutic combinations that build on the impact of JZP-815, a novel pan-RAF inhibitor that has been shown to boost the effect of other therapeutic agents used to treat NSCLC with KRAS mutations.

Read More

SU2C Research Portfolio (see page 114)

Eirini Papapetrou, MD, PhD, received a Blood Cancer Discoveries Grant from the Leukemia and Lymphoma Society for “GNAS as a New Therapeutic Target for MDS.” The Papapetrou Lab recently discovered a long isoform of the GNAS gene as a driver of myelodysplastic syndrome (MDS) with splicing factor mutations. This project will evaluate GNAS as a therapeutic target for MDS and acute myeloid leukemia. 

Jerry Edward Chipuk, PhD, received R01 funding from the National Cancer Institute for “Chronic Mitochondrial Division and Melanoma: Mechanism, Prognosis, and Therapy.” The goals of this study are to provide key mechanistic details into the process and contributions of mitochondrial dysfunction during oncogenic transformation, and develop novel translational tools focused on the detection and inhibition of chronic mitochondrial division to enhance cancer prognosis and treatment. 

Emily Gallagher, MD, PhD, received a MERIT Award (R37) from the National Cancer Institute for “Understanding How Elevated Triglycerides Contribute to Triple Negative Breast Cancer Growth and Metastasis.” The study will investigate whether starving triple negative cancer cells of high circulating triglycerides (found in more than half of women with triple negative breast cancer) can be exploited as a novel therapeutic strategy.

Elisa Port, MD, and Hanna Irie, MD, PhD, were awarded grant funding from the Breast Cancer Research Foundation to study the immune microenvironment of triple negative breast cancer and identify new strategies to enhance anti-tumor immune responses for these aggressive breast cancers. Dr. Port and Dr. Irie have been continuously funded for the past eights years through a competitive renewal process.

Nina Bhardwaj, MD, PhD, was awarded a Clinic and Laboratory Integration Program grant from the Cancer Research Institute for “Adaptive and Innate Immune Response Induced by Therapeutic PGV_001 Multipeptide Pesonalized Neoantigen Vaccine in Phase-I Clinical Trial, Across Various Types of Cancers in Adjuvant Setting.” The project aims to utilize state-of-the art technologies and assays to thoroughly interrogate the degree of anti-tumor immunity induced by the neoantigens in PGV_001. Data from the project will aid in the understanding of the mechanisms by which PGV_001 alters the immune response once the tumor burden is lifted and will help with design of combination treatments that complement neoantigen tumor vaccines. Mansi Saxena, PhD, is Co-investigator on the project.

Claudia Henschke, PhD, MD, Professor of Radiology, received the 37th Annual Alton  Ochsner Award Relating Smoking and Disease. The award recognizes scientists who have made major contributions to the relationship between smoking and disease and who have advanced the development of major prevention and treatment modalities. Dr. Henschke pioneered the use of low-dose CT screening for lung cancer.

In response to the many requests for participation, she created the International Early Lung Cancer Action Program, a global community of researchers, including more than 80 institutions with a common research agenda. As a result of her pioneering efforts, lung cancer screening has now achieved mainstream acceptance.

Read More

Natasha Kyprianou, MBBS, PhD, Professor of Urology, Oncological Sciences, and Pathology & Cell Based Medicine, was honored with the Presidential Medal of Distinction, bestowed by the President of the Republic of Cyprus, for her contributions to science and cancer research. A translational researcher in urologic oncology, Dr. Kyprianou focuses on dissecting the mechanisms of therapeutic resistance in lethal prostate cancer and development of targeted modalities to treat advanced disease. The award ceremony recognizing Dr. Kyprianou and ten others (including philanthropists and other leading physician-scientists globally) was held on July 28 at the Presidential Palace in Cyprus on the occasion of the World Conference of Diaspora.

Read More

Eimear Kenny, PhD, Professor of Medicine and Genetics, Director, Institute for Genomic Health, and TCI member, received the 2022 American Society for Human Genetics Early-Career Award, in recognition of her work to improve accessibility of genetics to global populations and advocate for expanding diversity in the genetics workforce.

Read More

Susanna Curtis, MD, PhD, joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology) and Assistant Director of the Mount Sinai Sickle Cell Disease Program. Dr. Curtis was most recently Assistant Professor at Albert Einstein College of Medicine and Assistant Director of the Montefiore Adult Sickle Cell Center. Dr. Curtis received her MD from New York Medical College and her PhD from Yale School of Medicine; she also has a MS in Physiology from Georgetown University.

Dr. Curtis completed residency in Internal Medicine at Montefiore, and fellowship in Hematology and Oncology and post graduate fellowship in Hematology at Yale. She is an editorial board member for Blood Advances, and holds current NIH grand funding for “Dronabinol for the Reduction of Chronic Pain and Inflammation in People with Sickle Cell Disease.”

Santiago Thibaud, MD, joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology). His specialty is multiple myeloma, and he works with the team at the Center of Excellence for Multiple Myeloma. Dr. Thibaud earned his MD from Centro de Educación Médica e Investigaciones Clínicas in Buenos Aires, Argentina. He completed Internal Medicine residency at Albert Einstein College of Medicine/Montefiore Medical Center, where he also served as Chief Resident. Dr. Thibaud did his fellowship training in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai. He received the Young Investigator Award for Exemplary Abstract at the 2021 International Myeloma Workshop and First Prize for Oral Presentation at Icahn Mount Sinai’s Annual Research Day in 2021.

Virginia Corbett, MD, joined the faculty at Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology), with a focus on neuroendocrine tumors and liver cancer. Dr. Corbett earned her MD from Michigan State University College of Human Medicine. She completed residency in Internal Medicine at New York-Presbyterian Hospital/Weill Cornell Medical College and fellowship in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai. She served as Chief Medical Resident at Memorial Sloan Kettering Cancer Center. Dr. Corbett is interested in developing clinical trials evaluating novel combinations of immunotherapy with other agents for neuroendocrine tumors and gastrointestinal cancers. She sees patients at the Ruttenberg Treatment Center.

The Division of Hematology and Medical Oncology welcomed eight first-year fellows in July. Click here for the roster.

Three medical students at the Icahn School of Medicine at Mount Sinai participated this summer in the TCI Summer Scholars Program, designed to provide opportunities to conduct original cancer research for medical students who have not yet had extensive research experience.

The 2022 scholars, their faculty mentors, and projects are:

Nina Rodriguez, mentored by Richard Bakst, MD

The Role of the Microbiome in Mediation Head and Neck Squamous Cell Carcinoma and Treatment Related Toxicity

Originally from Miami, Nina is a second year MD/MSCR student at the Icahn School of Medicine at Mount Sinai. Nina graduated from Princeton University, where she studied Political Science. She then worked for two years at the Boston Consulting Group (BCG) before starting medical school. 

Ayman Mohammed, mentored by Bridget Marcellino, MD, PhD

Targeted Protein Degradation of PPM1D in Myeloproliferative Neoplasms

Originally from Brooklyn, Ayman is a second year MD student at the Icahn School of Medicine at Mount Sinai. After graduating from Harvard College with concentrations in Economics and Global Health & Health Policy, he worked at Roivant Sciences, a NYC-based biotechnology company, where he developed a passion for oncology and drug development.

Joseph Portelli, mentored by James Ferrara, MD

Biomarker Identification for Prediction of Non-relapse Mortality in Patients with Graft Vs Host Disease

The Tisch Cancer Institute (TCI) supports five Shared Resources to encourage interdisciplinary collaboration and foster the translation of scientific discoveries into novel cancer therapeutics.

• Biostatistics
• Flow Cytometry
• Microscopy
• Mouse Genetics
• Human Immune Monitoring Center

Additionally, three new cores are currently on track for TCI integration and support:

• Biorepository and Pathology
• Bioinformatics for Next Generation Sequencing
• Biomedical Data Science and Informatics Service

Under the leadership of Jerry Edward Chipuk, PhD, the Shared Resources undergo continuous improvement through rigorous planning and evaluation mechanisms.

As a reminder, TCI members are required to acknowledge the Cancer Center Support Grant (P30-CA196521) awarded to TCI by the National Cancer Institute in all publications, grants, and awards that include data or services derived from the TCI Shared Resources to ensure tracking of impact.

For more information, visit the TCI Shared Resources webpage.

Parissa Tabrizian, MD; Matthew L. Holzner, MD; Sander S. Florman, MD; Myron Schwartz, MD; Josep Llovet, MD, PhD; and colleagues

Outcomes of liver transplant and downstaging for hepatocellular carcinoma

JAMA Surgery. 2022 Jul 20. PMID: 35857294

In a large, multicenter cohort of patients with hepatocellular carcinoma (HCC) successfully downstaged to within Milan criteria (MC), 10-year post-liver transplant (LT) outcomes were excellent, validating national downstaging policies and showing a clear utility benefit for LT prioritization decision making. Surgical management of HCC recurrence after LT was associated with improved survival in well-selected patients and should be pursued, if feasible.

Press Release

Charles Powell, MD, MBA, and colleagues

Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies

ESMO Open. 2022 Aug 1. PMID: 35963179

Using data from nine phase I and II trastuzumab deruxtecan (T-DXd) monotherapy clinical trials, this study provides one of the most comprehensive analyses of interstitial lung disease (ILD)/pneumonitis in patients treated with T-DXd, an antibody drug conjugate designed as a targeted therapy for cancers. The retrospective review examined 1,150 heavily pre-treated patients with breast, lung, gastric, colorectal or other cancers. Study results suggest that close monitoring and proactive management may reduce the risk of ILD, and emphasize the importance of awareness and education to aid in early detection.

Press Release

Hideo Watanabe, MD, PhD; Charles Powell, MD, MBA; Mary Beth Beasley, MD; and colleagues

Transcriptional circuitry of NKX2-1 and SOX1 defines an unrecognized lineage subtype of small cell lung cancer

American Journal of Respiratory and Critical Care Medicine. 2022 Jul 18. PMID: 35848993

The current molecular classification of small cell lung cancer (SCLC) based on expression of four lineage transcription factors still leaves its major subtype SCLC-A as a heterogeneous group, necessitating more precise characterization of lineage subclasses. In this study, the researchers comprehensively describe additional epigenomic heterogeneity of the SCLC-A subtype, and define SCLC-Aα subtype by the core regulatory circuitry of NKX2-1 and SOX1 super-enhancers and their functional collaborations to maintain neuronal linage state.

Christian Rolfo, MD, PhD, and colleagues

External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer

ESMO Open. 2022 Aug 1. PMID: 35930972

Data for selpercatinib—a selective REarranged during Transfection (RET) inhibitor—from a single-arm trial (LIBRETTO-001, NCT03157128) in RET-fusion-positive advanced/metastatic non-small-cell lung cancer were used in combination with external data sources to estimate comparative efficacy in first- and second-line treatment settings. Results demonstrate statistically significant improvement in clinical outcomes associated with selpercatinib treatment. The findings will undergo confirmation with forthcoming results from an ongoing phase III randomized trial (LIBRETTO-431, NCT04194944).

Hannah Levavi, MD; Ronald Hoffman, MD; Bridget Marcellino, MD, PhD

JAK inhibitors in the treatment of myelofibrosis

Clinical Advances in Hematology & Oncology. 2022 Jul. PMID: 35803878

JAK inhibitors (JAKis) are the greatest advance in the treatment of myelofibrosis (MF) in the past decade. However, they do not halt disease progression and they are not tolerated by all patients. In this paper, the authors review both the U.S. Food and Drug Administration-approved JAKis and those in late-phase clinical trials for myelofibrosis (MF), with a focus on clinical activity and adverse effects. They also provide a schema for choosing among options for patients with MF.

Sacha Gnjatic, PhD, presented Novel Assays for Deep Immunoprofiling: Spatial and Single Cell Transcriptomics on July 21 at the 5th Annual Immuno-Oncology Coordination Forum for the Partnership for Accelerating Cancer Therapies (PACT).

Forum Agenda 

Upcoming Seminars

Cancer Biology Retreat

Department of Oncological Sciences

Monday, October 3, 8:30 am - 5 pm

The Ruth and Harold D. Uris Center for Education

The Metropolitan Museum of Art

***********

OncLive State of the Science Summit: Multiple Myeloma

Ajai Chari, MD, Chair

Wednesday, October 12, 6 -9 pm

Venue to be Announced

Registration Link

The Mount Sinai Health System Bereavement Committee will hold its

annual system-wide Memorial Service on October 12 at 12 pm

and October 27 at 6 pm to remember and celebrate the lives of

cancer patients who passed away this year.

Zoom Information

https://mssm.zoom.us/j/81322120216

ID: 813 2212 0216

Passcode: 304537

Phone: 646-931-3860