February 2021
Featured Research & Publication
Cell Stem Cell. 2021 Feb 10. PMID: 33571445

Eirini Papapetrou, MD, PhD, and colleagues report in Cell Stem Cell on the creation of the first cellular model that enables genomic tracking of the evolution of acute myeloid leukemia (AML). Constructed via CRISPR and induced pluripotent stem cell (iPSC) technologies, the model characterizes the molecular changes that underlie disease progression, and identifies dysregulation of inflammatory and innate immunity signaling as an early event in disease development that could provide a potential therapeutic target.
“By creating the first cellular model to track the evolution of human leukemia, we believe we’ve taken an important step toward unraveling the cellular biology of this disease,” said Dr. Papapetrou. “We’ve identified molecular vulnerabilities that occur early in the disease process which could potentially lead to improved biomarkers and novel treatments for AML—goals that have proven so elusive to medical science in the past.”

Grant Awards
Michelle K. Kim, MD, PhD, has been awarded research funding from the Neuroendocrine Tumor Research Foundation. Dr. Kim is using stage and tumor grade data along with innovative digital image analyses to evaluate how orphometric feature analysis may improve clinicians’ ability to predict outcomes for patients with gastroenteropancreatic neuroendocrine tumors.
Jose Javier Bravo-Cordero, PhD, and Deanna Benson, PhD, have received a grant award from the Michael J. Fox Foundation. Their funded research will focus on understanding the biology that drives the increased risk for melanoma observed in people with Parkinson’s Disease. Using mouse models and intravital microscopy, Dr. Bravo-Cordero and Dr. Benson will test how a common Parkinson's Disease gene mutation alters the melanoma microenvironment and disease progression.
Honors and Awards
Exceptional Care for Patients with Thoracic Malignancies

The Mount Sinai Health System was honored by the International Association for the Study of Lung Cancer (IASLC) as the 2020 North American recipient of the IASLC Cancer Care Team Award (CCTA). The CCTA recognizes a single institution in North America, Europe, Latin America and Asia/Rest of the World that provide exceptional care for patients with lung cancer and thoracic malignancies. Of the four teams, Mount Sinai was selected as the overall winner.

“Oftentimes delivery of patient care is at its best when multidisciplinary team members offer the patient seamless and informed communication, as well as an individualized treatment plan based on not just the patient’s needs but the patient’s wishes,” said Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology.

Team members: Andrea Wolf, MD: Marissa Senise, NP; Jorge Gomez, MD; Jessica Fernandez, PA; Thomas Marron, MD, PhD; Stephanie Lehrman LCSW; Kenneth Rosenzweig, MD

Cancer Screening Expansion
Mobile MRI Unit for Prostate Screening

A mobile MRI unit to support prostate health in the Black community, which experiences a high incidence of prostate cancer, will launch at the end of the summer. The Robert F. Smith Mobile MRI Unit, named for the funding donor, will provide prostate screening in highly concentrated Black neighborhoods across New York City. Follow-up visits with Mount Sinai Health System urologists will be scheduled as needed.

Image credit: American Cancer Society
Research Showcased in Videos
Videos created by the Graduate School of Biomedical Sciences
for the PhD student interview process feature research advancements and opportunities.

The Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai offers top-ranked PhD, Master’s, Dual-Degree, and Specialty programs for students looking to make strategic and meaningful connections between science, medicine, education, and health care delivery.
Science Advances. 2021 Jan 29. PMID: 33514539

The researchers explored the previously undescribed role of L-Myc and c-Myc—members of the MYC family of basic helix-loop-helix (bHLH) transcription factors—as lineage-determining factors contributing to small cell lung cancer (SCLC) molecular subtypes and histology. The Myc family has historically been grouped as general oncogenes. The data from this research suggest that the role of the Myc family in SCLC tumorigenesis could be redefined, providing new insight into currently proposed molecular subtypes of SCLC in order to develop more personalized strategies for effective therapies.

Urologic Oncology. 2021 Feb. PMID: 33262028

In this review the researchers discuss the role of Bacillus Calmette-Guerin (BCG)—the only FDA approved first line therapy for patients with non-muscle-invasive bladder cancer—as a vaccine and the known immune pathways that are activated by intravesical BCG. They examine what can be harnessed from previous studies of BCG-trained immunity in settings of microbial pathogens, and outline a potential clinical study integrating BCG vaccination prior to intravesicle administration of BCG.

Journal for Immunotherapy of Cancer. 2020 Dec. PMID: 33428584

The researchers review the activity of natural killer (NK) cells in head and neck squamous cell carcinoma (HNSCC), paying special attention to the role of environmental and genetic determinants of NK cell antitumor function. They explore the evidence that NK cells are a crucial determinant of the efficacy of both established and emerging treatments for HNSCC.

Nature Reviews Gastroenterology & Hepatology. 2021 Jan 28. PMID: 33510460

In this review, the researchers analyze data from randomized and uncontrolled studies reported with ablative and imaging-guided liver tumor-directed procedures to treat hepatocellular carcinoma (HCC), and examine the expected effects of combinations with systemic treatments. They discuss trial design and benchmarks to be used as a reference for future investigations for combinations of local and systemic therapies for the treatment of HCC.

American Journal of Clinical Oncology. 2021 Jan 6. PMID: 33417323

This study evaluates the characteristics and patterns of emergency room (ER) and inpatient (IP) utilization among cancer patients with solid tumors receiving immune checkpoint inhibitor (ICI) therapy. The study identified a number of demographic and clinical factors associated with ER/IP care during ICI therapy, thereby informing preventive strategies and policies. Findings advance the understanding of factors highly relevant to patient-centered outcomes, health care disparities, and health services research.

Nature Reviews Disease Primers. 2021 Jan 21. PMID: 33479224

This primer provides an update on the advancements in hepatocellular carcinoma (HCC) pathogenetic mechanisms and its treatment. It describes evidence-based data generated with new therapies and the prospects of novel combination therapies, as well as the role of biomarkers and liquid biopsy in the future management of HCC. 

Hematology/Oncology Clinics of North America. 2021 Jan 27.

This review provides insight into novel, mechanisms-based targeted therapies for myelofibrosis (MF) that are under clinical evaluation, thanks to advances in next-generation sequencing and expanded understanding of the molecular underpinnings of MF. Preclinical modeling supports an emphasis on non-JAK pathway-based targeted approaches, combination therapy regimens, and modulation of the tumor microenvironment.

Nature Reviews Drug Discovery. 2021 Jan 19. PMID: 33469207

Deregulation of the enzymes or "writers" of protein lysine methylation, lysine methyltransferases (KMTs), is implicated in the cause of many diseases, including cancer. In this review, the authors discuss the disease relevance of KMTs, focusing on the two KMTs that have been most extensively characterized as drug targets and for which inhibitors have been tested in the clinic: enhancer of zeste homologue 2 (EZH2) and disruptor of telomeric silencing 1-like protein (DOT1L). They also discuss inhibitors that target writers that have shown promise in preclinical studies as well as the development of drugs to target KMTs for which inhibition has clear therapeutic potential.

Clinical Cancer Research. 2021 Jan 8. PMID: 33419780

This overview presents strategies for a systematic approach to biomarker identification and correlation with clinical outcomes across clinical trials to improve immunotherapy approaches for cancer patients. It highlights assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. 
Hematology and Medical Oncology Grand Rounds
Evert E. Vokes, MD, John E. Ultmann Professor; Chairman, Department of Medicine; Physician-in-Chief, University of Chicago Medicine and Biological Sciences
“De-escalating Curative Therapy for Advanced Head and Neck Cancer”

James N. Kochenderfer, MD, Senior Investigator, Surgery Branch, Center for Cancer Research, National Cancer Institute
“Chimeric Antigen Receptor T-cell Therapy for Hematologic Malignancies”

Translational Oncology Seminars
Brooke Emerling, PhD, Assistant Professor, Cancer, Molecules and Structure Program, Sanford Burnham Prebys Medical Discovery Institute
“Targeting Non-canonical Phosphoinositide Signaling for Metabolic Homeostasis”

Alessandro Lagana, PhD, Assistant Professor, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
‘Computational Modeling of Multiple Myeloma: From Disease Subtypes to Novel Biological Insights”

TCI Seminar Series
Gad Getz, PhD, Director, Cancer Genome Computational Analysis, Broad Institute
Grateful Patient
“Dr. Jagannath has always been available to answer questions or talk about my concerns,” said Suzanne Wetanson. “He made me feel secure, safe, and comfortable.”

Do you have news for the next issue of TCI Connections

Please send to Janet Aronson (646-745-6376)

Remember to share breaking news and high impact news that might be appropriate for media coverage with Marlene Naanes (929-237-5802) in the Press Office. This may include pending FDA drug/device approvals, studies/trial results being published in high-impact journals, and patient stories. The more lead time you can give Marlene, the better—ideally, four weeks or when a paper is accepted by the journal. Embargoes will always be honored and news will only be released with your approval.
  TCI Connections  is a monthly publication of The Tisch Cancer Institute
Ramon Parsons, MD, PhD, Director
Janet Aronson , Editor
Past issues of  TCI Connections  are available on the TCI website