May 2023

Eirini Papapetrou, MD, PhD, and colleagues

Patient-derived iPSCs faithfully represent the genetic diversity and cellular architecture of human acute myeloid leukemia 

Blood Cancer Discovery. 2023 Apr 17. PMID: 37067914

Dr. Papapetrou and team report on the first powerful models that are nearly identical to acute myeloid leukemia (AML) in humans. They developed a reprogramming method tailored to cancer cells, with which they generated induced pluripotent stem cells (iPSCs) from patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. The results demonstrate that xenotransplantation selects for effectively identical cells between primary and AML-iPSC-derived leukemia cells. The diverse panel of AML-iPSCs and associated transcriptome data generated from this research is a valuable resource for basic and preclinical studies of AML and other human cancers.

Press Release

Schematic representation of the experimental design

Deborah Doroshow, MD, PhD, was sworn in as an honorary police surgeon with the NYPD Ceremonial Unit in March. In this role, Dr. Doroshow will serve as a resource for NYPD employees and family members receiving care for cancer at Mount Sinai.

Edgar Gonzalez-Kozlova, PhD, Assistant Professor of Oncological Sciences, won a scholarship to attend the annual meeting of the International Society for Extracellular Vesicles. He will present his work, done in collaboration with Navneet Dogra, PhD, and Sacha Gnjatic, PhD, that focuses on characterizing the molecular contents of extracellular vesicles and particles (EVPs) that contain immune related RNA signatures; these EVPs can be isolated from tissue and blood in the context of genitourinary cancers to be used as prognostic biomarkers.



In parallel, Dr. Gonzalez-Kozlova was invited by the Extracellular RNA Communication Consortium to present a part of his work on EVPs that involves the development of novel computational approaches to characterize EVP-derived RNAs. The talk is available online. 

Fred R. Hirsch, MD, PhD, has joined the Editorial Board of AME Medical Journal.

Eirini Papapetrou, MD, PhD, is the founding Director of the new Center for Advancement of Blood Cancer Therapies (CABCT), co-sponsored by the Institute for Regenerative Medicine and The Tisch Cancer Institute. The mission of the CABCT is to accelerate the development of new therapies for blood cancers and other blood diseases.

Related Press Release

Joshua Brody, MD, received a Follicular Lymphoma Priority Research Grant award from the Lymphoma Research Foundation. Dr. Brody will investigate whether inhibiting regulators of tumor death receptor signaling (e.g., Fas) can potentiate bystander killing of antigen-negative lymphoma cells to prevent relapse after T cell-based immunotherapies such as CAR T-cell therapy and bispecific antibodies. If successful, this approach could yield long-lasting remissions for patients.

Joseph Sparano, MD, and William Fraser Symmans, MD, at MD Anderson, received a U.S. Department of Defense clinical research extension award for follow-up work on TAILORx and RxPONDER—landmark NCI-sponsored breast cancer clinical trials that achieved their primary objectives in prospectively validating the prognostic and predictive role of the 21-gene Oncotype DX RS assay in guiding adjuvant chemotherapy use. Goals of this project are to have extended follow-up for both trials and to perform a prospective validation study of a new gene expression test (Sensitivity to Endocrine Therapy (SET) Index) to enable greater personalization of adjuvant therapy. Upon completion of the project, it is expected that the 21-gene RS and SET Index will be used in combination to guide use of adjuvant chemotherapy with greater precision than currently possible with the RS alone, sparing additional patients unneeded chemotherapy, and identifying some who would derive a chemotherapy benefit but otherwise would not have been advised to receive chemotherapy based on the RS results alone. 

Jerry Edward Chipuk PhD, is the lead investigator on a new Multiple Principal Investigator R01 award from the National Cancer Institute—“The Oncogene Activated Mitochondrial Unfolded Protein Response Regulates Senescence Biology”—in collaboration with Julide T. Celebi, MD, at NYU Langone Health. The study focuses on the role of oncogene-induced mitochondrial stress as a key determinate in early disease melanoma, with an overarching goal to learn more about how mitochondria control melanocyte fate and the immune landscape. Findings may reveal novel prognostic markers and therapeutic targets for melanoma and other mutant RAS/BRAF positive cancers.

Awards from the Melanoma Research Alliance (MRA) 

Diego Chowell, PhD, is the recipient of a Young Investigator Award from the MRA for “Dissecting the Dynamic Immune Ecosystem During Melanoma Evolution.” This project aims to investigate the reciprocal interactions between the tumor genome and its immune microenvironment during carcinogenesis, which will reveal important immunoediting mechanisms driving elimination, equilibrium, and escape.

Poulikos Poulikakos, PhD, is the recipient of a Pilot Award from the MRA for “A Drug-binding Assay Platform to Optimize Therapies for RAS-mut Melanomas.” The project aims to develop drug-binding assays in cells that would eventually enable the rational design of combination therapies targeting MAPK signaling with high therapeutic synergy and minimal on-target toxicities for RAS-mutant melanomas.

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Eirini Papapetrou, MD, PhD, received a R01 grant from the NCI titled “Mechanisms and Targeting of Aberrant Gas Activation in Myeloid Neoplasms.” Myelodysplastic syndromes (MDS) are myeloid neoplasms with dismal prognosis, frequent progression to acute myeloid leukemia (AML), and no effective treatment. The goal of this project is to investigate G⍺s, the alpha subunit of the stimulatory G protein, as a therapeutic target for MDS with splicing factor mutations and identify opportunities for therapeutic interventions that inhibit its activation or downstream signaling. This work can establish a new therapeutic target and lead to novel therapies that can transform the treatment of MDS, AML, and possibly other cancers.

A new clinical trial—A Phase II Study of the Effects of Pembrolizumab on Quality of Life for Patients With Treatment-Naïve, Advanced or Metastatic NSCLC and Poor Performance Status—will examine the effects of first-line pembrolizumab on quality of life, efficacy, and toxicity for people with newly-diagnosed locally-advanced or advanced non-small cell lung cancer who have a performance status of 2-3 and whose cancer has a PD-L1 tumor proportion score of at least 1%. PD-L1 inhibitors like pembrolizumab are often used in this context but with very little prospective data available about its clinical impact. This study hypothesizes that pembrolizumab will improve patient-reported quality of life as measured by the EORTC QLQ-C30. It was designed by Bailey Fitzgerald, MD, third year hematology/oncology fellow, under the mentorship of Deborah Doroshow, MD, PhD. 

Search here for cancer clinical trials by disease site/cancer type, investigator, or trial phase.

The Biostatistics & Clinical Informatics Shared Resource (BCISR)—created from the unification of Biostatistics with the Biomedical Data Science and Informatics Service—ensures availability of biostatisticians with expertise in diverse cancers and statistical methodologies who work with TCI members to curate, compile, and analyze data and assist with manuscript preparation. Directed by Madhu Mazumdar, PhD, BCISR also manages structured access to reliable clinical data to foster population science and clinical research studies.

For more information, contact Dr. Mazumdar (Madhu.mazumdar@mountsinai.org) or Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.

Tiphaine Martin, PhD; Ramon Parsons, MD, PhD; and colleagues

B7-H3 drives immunosuppression and Co-targeting with CD47 is a new therapeutic strategy in β-catenin activated melanomas

Pigment Cell & Melanoma Research. 2023 Apr 21. PMID: 37086018

Melanomas with activated β-catenin represent a subtype associated with T-cell non-inflamed tumor (cold tumor) microenvironment and poor responses to anti-PD-1 and anti-CTLA-4 therapy. Using a preclinical mouse model of activated β-catenin, the research team identified a co-targeting strategy (anti-CD47) that can be combined anti-B7-H3 treatment. The study suggests that B7-H3 and CD47 drive distinct signaling pathways in shaping the tumor microenvironment and their combined blockade results in cooperative cytotoxicity, providing a rationale for clinical co-targeting of B7-H3 and CD47, in β-catenin activated melanomas.

Matthew Park, Ivan Reyes-Torres, Miriam Merad, MD, PhD, and colleagues

TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer

Nature Immunology. 2023 May. PMID: 3701148

Dr. Merad and team investigated the role that triggering receptor expressed on myeloid cells 2 (TREM2) plays in the development of non-small cell lung cancer (NSCLC). They found that phagocytic sensing of tumor cell-derived antigens triggers the TREM2 program in murine monocyte-derived macrophages (mo-macs), which then promoted the transition of mo-macs toward a pro-tumorigenic state. TREM2 blockade unleashed natural killer (NK) cell immunity and significantly eliminated tumors. Dr. Merad and team propose that TREM2 on mo-macs is a major immune checkpoint that mutes NK-cell-mediated antitumor immunity in NSCC. The ability for TREM2⁺ mo-macs to regulate NK cells provides a strong rationale for the clinical development of combinatorial therapies that concurrently inhibit TREM2 and enhance NK cells.

Avi Ma’ayan, PhD, and Lab

Computational screen to identify potential targets for immunotherapeutic identification and removal of senescence cells

Aging Cell. 2023 Apr 20. PMID: 37082798



To prioritize gene and protein candidates that may enable the selective identification and removal of senescent cells, Dr. Ma’ayan and team compared gene expression signatures from replicative senescent cells to transcriptomics and proteomics atlases of normal human tissues and cell types. A gene set made of 301 genes called SenoRanger was established based on consensus analysis across studies and backgrounds. Pathway analysis that connected the SenoRanger genes to their functional annotations confirms their potential role in several aging and senescence-related processes. Overall, SenoRanger provides solid hypotheses about potentially useful targets for identifying and removing senescence cells.

Yichen Zhong, BS; Shi Du, MS; Yizhou Dong, PhD

mRNA delivery in cancer immunotherapy

Acta Pharmaceutica Sinica B. 2023 Apr. PMID: 37139419



In this review, Dr. Dong and team introduce four categories of nanoparticle platform systems—lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles—along with their roles in facilitating mRNA-based cancer immunotherapies. They also highlight promising treatment regimens and their clinical translation.

Rima Patel, MD; Paula Klein, MD; Amy Tiersten, MD; Joseph Sparano, MD

An emerging generation of endocrine therapies in breast cancer: a clinical perspective

NPJ Breast Cancer. 2023 Apr 5. PMID: 37019913

This review addresses the recent emergence of several anti-estrogen therapies that are being evaluated in both early and metastatic settings. The authors discuss the efficacy, toxicity profile, and completed and ongoing clinical trials for each drug and highlight key differences in their activity and study population that have ultimately influenced their advancement.

Fred Hirsch, MD, PhD, is Co-editor of Artificial Intelligence in Thoracic Disease, a collection of review and research articles covering AI applications in radiology, pathology, pulmonary medicine, surgery, oncology, and radiation oncology.

Nina Bhardwaj, MD, PhD, was a Keynote Speaker at Frontiers in Cancer Immunotherapy 2023, conducted by the New York Academy of Sciences, May 2-4. The title of Dr. Bhardwaj’s address was “Properties of Tumor Antigens Determining Induction of Immunity.”

Laurie Margolies, MD, gave a talk on breast arterial calcification at a plenary session at the annual symposium of the Society of Breast Imaging, held May 4-7. She was also an invited participant in Breast Imaging Jeopardy.

Presentations by radiology residents working with Dr. Margolies and colleagues included:

• Clara Koo, MD, and Anthony Yang, MD: abstract analyzing the accuracy of AI for breast ultrasound
• Sarah Ameri, MD; Siya Patel, MD; Divya Gupta, MD: educational abstract on the use and potentials of social media in breast imaging

Also, Emma Klein, fourth year medical student, presented an oral abstract analyzing usage of and delayed cancer diagnoses on breast MRI exams read as BI-RADS 3 and an electronic abstract on the effects of BI-RADS 4 and 5 MRI readings on extent of disease evaluations.

Jennifer Marti, MD, and Tara Balija, MD, presented posters at the annual meeting of The American Society of Breast Surgeons, April 26-30.

• Dr. Marti: "Radiographic Progression of Atypical Lobular Hyperplasia on Needle Core Biopsy Undergoing Active Surveillance"
• Dr. Balija: "Autologous Breast Reconstruction is Associated With Post Mastectomy Chest Wall Lymphedema" (primary investigator: Stephanie Bernik, MD)

Hematology/Medical Oncology Grand Rounds

Gedalio and Sonia Grinberg/Nathaniel Wisch, MD, Endowed

Visiting Lectureship

Amit Verma, MD, Montefiore Medical Center

“Therapeutic Targeting of MDS”

May 25, 8:30 am, Hess Seminar Room B

Mount Sinai Genomic Health Initiative, Thought Leader Speaker Series

Katherine A. High, MD

Visiting Professor, Rockefeller University

Professor Emerita, Perelman School of Medicine, University of Pennsylvania

"Turning Genes Into Medicines: Highlights and Hurdles in the Development of Gene Therapy for Genetic Disease"

June 2, 4 - 5:30 pm, Hatch Auditorium

Register

Save the Date - TCI Community Outreach and Engagement Retreat

September 29, 10 am - 1:30 pm

Annenberg Building, 5-205

Also via Zoom

Register

Attendee Information

Mount Sinai received a grant for the second consecutive year from the American Cancer Society to assist with the provision of transportation at all Mount Sinai locations for cancer patients identified by oncology social workers. This grant helps the Tisch Cancer Institute’s Community Outreach and Engagement Program address cancer disparities and ease the burden of cancer for patients and families.

ACS Press Release

Rima Patel, MD, Chief Fellow, Hematology and Medical Oncology, received a 2023 ASCO Annual Meeting Merit Award from Conquer Cancer (the ASCO Foundation) for her abstract, "Utility of Ki67 in Guiding Adjuvant Abemaciclib Therapy for Patients With Hormone Receptor (HR)-positive, Early Breast Cancer (EBC)," to be presented at the annual ASCO meeting in June. Dr. Patel’s mentors for this project are Amy Tiersten, MD, and Joseph Sparano, MD.

Award Recipients

Tarek Mouhiuddine, MD, Fellow in Hematology and Medical Oncology, was selected as a recipient of the 2023 ASH Research Training Award for Fellows (RTAF) from the American Society of Hematology. The RTAF provides research funding to fellows and is designed to encourage junior researchers to continue scientific pursuits focused in the blood sciences.

Dr. Mouhieddine conducts research on multiple myeloma in the laboratory of Samir Parekh, MD.

TCI has become an American Statistical Association (ASA) ally by supporting the ASA’s Diversity Mentoring Program (DMP) and StatFest. DMP brings together historically underrepresented undergraduate and graduate students, post-docs, and early career professionals with senior statisticians for mentoring, networking, and leadership and skills development. StatFest, to be held on September 23, is a one-day conference for undergraduate students designed to help them understand opportunities and routes for success in statistics. Madhu Mazumdar, PhD, Director of TCI’s Biostatistics & Clinical Informatics Core, is on the planning committee for both DMP and StatFest.

Four medical students at the Icahn School of Medicine at Mount Sinai have been selected for the 2023 TCI Summer Scholars Program. Directed by Janice Gabrilove, MD, Jenny Lin, MD, MPH, and James Ferrara, MD, the program provides stipends for students to conduct original cancer research under the mentorship of a TCI faculty member.

The students/mentors and projects are:

• Annie Chang/Emma Guttman, MD, PhD; Nicholas Gulati, MD, PhD: “Transcriptomic Profiling of the Immune and Barrier of Sclerotic-type Chronic Graft-Versus-Host Disease (ScGVHD) Tape Strips”
• Carlos Ortega Rios/James Ferrara, MD: “GVHD Severity, Serum Biomarkers, and Long-term Outcomes in African American Patients Following HCT”
• Catherine Yu/Maaike van Gerwen, MD, PhD: “Prognostic Value of Primary Site in Cutaneous Head and Neck Melanoma”
• Shubham Gulati/Emanuela Taioli, MD, PhD: “The Impact of Lung Cancer Treatment on the Severity of Subsequent COVID-19 Infections”

Related article in Journal of Cancer Education