DISCOVERIES AND DEVELOPMENTS At The Tisch Cancer Institute, we are dedicated to translating our basic science findings into clinical applications, with a focus on providing the most comprehensive and effective care for cancer patients. The 2019 Specialty Report for The Tisch Cancer Institute features many of our latest discoveries and developments that are advancing precision-medicine therapeutics and optimal outcomes for patients, including: Novel Class of Drugs for Myeloproliferative Neoplasms Ronald Hoffman, MD , and John Mascarenhas, MD , are investigating a molecule that could inhibit the activity of MDM2 and MDM4, both implicated in cancer cell proliferation.   Targeting the Root of Metastasis William Oh, MD , and Julio Aguirre-Ghiso, PhD , are looking at drug combinations that can target cancer dormancy, making them unable to metastasize. Related article: Breast Cancer Research Improving Prognosis for Melanoma Patients Findings reported by Emily Bernstein, PhD, in Nature Communications demonstrate a potential approach to preventing drug resistance by inhibiting the effects of BRAF mutations and IGFBP2-driven biological pathways.   Therapeutic Targets for Aggressive p-53-like Bladder Cancer Matthew Galsky, MD , and Jun Zhu, PhD , have identified microRNA biomarkers as potential prognostic markers. Related articles: Oncogene , Nature Communications Read More

You are cordially invited to a special ASCO Mount Sinai reception hosted by: Ramon E. Parsons, MD, PHD Director, The Tisch Cancer Institute William Oh, MD Deputy Director, The Tisch Cancer Institute

HONORS AND GRANT AWARDS

Distinction of Service Matthew Galsky, MD , was named a 2019 Fellow of the American Society of Clinical Oncology (ASCO). This distinction recognizes ASCO members for their extraordinary volunteer service, dedication, commitment to ASCO, and efforts on behalf of the patients they serve. The award ceremony will take placed at the annual ASCO meeting , May 31-June 4.

Concepts in Lung Cancer Zeynep H. Gümüş, PhD , has been granted a Department of Defense Lung Cancer Research Program (DOD LCRP) Concept Award for “Identifying mutational signatures of military carcinogens in lung adenocarcinomas of service members and veterans.” The Concept Award supports highly innovative, untested, potentially groundbreaking concepts in lung cancer.   Recent whole-exome and -genome sequencing studies, including The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), have provided tremendous insights into the genomic makeup of non-small cell lung adenocarcinoma (LAD) tumors. These studies have identified a number of mutational signatures suggesting that tumors carry an imprint of the environmental agents to which patients were exposed. While tobacco smoke is the principal agent that causes lung cancer in civilians, military service members can be exposed to a variety of carcinogens whose imprints are unknown. This research project will utilize whole-genome sequencing (WGS) to determine the full spectrum of genomic alterations in tumors of LAD individuals who were exposed to jet fuel during military service. The genetic alterations will be characterized and compared to publicly available LAD (TCGA, ICGC) WGS datasets to identify their exposure-specific mutational signatures and cancer drivers, with the goal of advancing prognostic and therapeutic potential.   As a cancer geneticist, Dr. Gümüş develops and applies computational methods and tools to identify genetic drivers of tumor initiation and progression. She joined Mount Sinai in 2014 as an Assistant Professor in the Department of Genetics and Genomic Sciences and the Icahn Institute for Data Science and Genomic Technology .

Preventing Tumor Progression Nadejda Tsankova, MD, PhD , received an R01 grant award for “ Crosstalk between EGFR and TEAD Activity Directs Migration in Human Glioblastoma.”   Understanding the exact mechanisms by which glioblastoma cells infiltrate deep into the brain, evading surgical resection and chemotherapy, is needed in order to prevent tumor progression. Our research will explore the role of transcription factors as drivers of the migratory tumor cell state, focusing on the TEAD family of regulators and their relationship to EGFR signaling, using CRISPR-knockout and pharmacological inhibition in primary patient-derived glioblastoma cells and in immunocompetent and xenograft mouse glioma models. We will test the potential therapeutic efficacy of YAP-TEAD inhibitors, with the expectation that pharmacologic inhibition of glioblastoma infiltrative growth will alleviate tumor burden while also blocking oncogenic RTK effects, thus offering new therapeutic options.   Dr. Tsankova is Associate Professor of Pathology and Neuroscience. Her laboratory conducts research on characterizing the molecular mechanisms of progression in glioblastoma, with a focus on the role of epigenetic and transcriptional regulators for maintaining cancer stem-cell states and tumor migration.

FACULTY NEWS

Benjamin Hopkins, PhD , joined Mount Sinai in March as Assistant Professor in the Departments of Oncological Sciences and Genetics and Genomic Sciences. Dr. Hopkins’ focus is on translational research through the development of an organoid-based functional genomics platform. He will use personalized models of cancer to identify cancer-specific vulnerabilities, elucidating the molecular mechanisms that underpin treatment efficiency and examining how systemic metabolism impacts tumor initiation and disease progression. Dr. Hopkins received his PhD in Biology from Columbia University. He was most recently an Instructor in the Cantley Laboratory at Weill Cornell Medicine.

NEW ROLES

Joseph Finkelstein, MD, PhD , Chief Research Informatics Officer (CRIO) and Senior Associate Dean, Icahn School of Medicine at Mount Sinai, has been named Associate Director of Cancer Information Technology for The Tisch Cancer Institute. As CRIO and Senior Associate Dean, Dr. Finkelstein oversees Mount Sinai information technology (IT) needs related to research, taking advantage of the unique data assets, diverse patient population, and informatics resources of the entire Mount Sinai Health System. As Associate Director of Cancer IT, Dr. Finkelstein will work to catalyze cancer research by advancing comprehensive IT infrastructure to support intelligent data aggregation, predictive analytics, and conduct of clinical trials.   Dr. Finkelstein’s current studies focus on tailored interactive patient engagement in personalized health; pharmacogenomic support for medication optimization; and analysis of heterogeneous health information datasets for building individualized patient care prediction models.   Fred R. Hirsch, MD, PhD , an internationally-renowned authority on lung cancer treatment and research who joined Mount Sinai Health System in 2018, is the Executive Director of the newly-created Center for Thoracic Oncology in The Tisch Cancer Institute. He is also the Joe Lowe and Louis Price Professor of Medicine and will be the Associate Director of Biomarker Discovery for The Tisch Cancer Institute. Press Release Previous TCI Connections announcement

PUBLICATIONS

Analysis of chromatin accessibility uncovers TEAD1 as a regulator of migration in human glioblastoma

Nadejda Tsankova, MD, PhD Nature Communications Glioblastoma (GBM), the most common primary brain tumor in adults, has a dismal prognosis, in part due to the diffusely infiltrative nature of tumor growth and the poor response to chemotherapy of glioma cells that have migrated away from the tumor’s core. In this study, we utilized a recently developed protocol for the prospective isolation of human stem cells from GBM (GSCs) and neural/progenitor cells directly from GBM in order to examine the intrinsic transcriptional regulators of tumorigencity. We defined transcriptionally accessible regions unique to GSCs that specifically related to cell migration and which are highly enriched for TEAD1/4 motifs, provided functional validation for the role of TEAD1 in GBM migration, and showed that TEAD1 directly regulates AQP4 expression to promote cell migration.

Clinicopathologic and Genomic Factors Associated With Oncologic Outcome in Patients With Stage III to IV Chromophobe Renal Cell Carcinoma

Ketan Badani, MD Clinical Genitourinary Cancer A small subset of chromophobe renal cell carcinoma (chRCC), known as an indolent tumor, behaves in a clinically aggressive manner. Patients with recurrent chRCC demonstrated a differential gene expression of specific biochemical pathways than patients with nonrecurrent chRCC. The most commonly overexpressed pathways were neuroactive ligand-receptor interactions and cytokine-cytokine receptor interactions. The most activated gene functions were cellular, metabolic, and multicellular organismal processes. These expression patterns, as well as clinical parameters associated with worse overall survival, can potentially be used as novel biomarkers to identify aggressive variants of chRCC.

Rare, Pathogenic Germline Variants in Fanconi Anemia Genes Increase Risk for Squamous Lung Cancer

Zeynep H. Gümüş, PhD Clinical Cancer Research We identified rare, pathogenic germline variants in Fanconi Anemia (FA) genes as risk factors for increased risk of squamous lung cancer (SqCC). Our findings increase our understanding of SqCC predisposition and can be used toward development of a genetic diagnostic test to identify high-risk individuals who can benefit from personalized intensive surveillance, early detection and prevention strategies.

A Transcriptomic Signature of Tertiary Gleason 5 Predicts Worse Clinicopathological Outcome

Ashutosh Tewari, MD BJU International This study is the first that correlates TP5 with higher metastatic tumor potential, evaluated by means of the Decipher (R) score. This corroborates clinical observations for which patients with Gleason 7 with TP5 harbor poorer prognosis with respect to their counterpart without TP5. Our study also represents the first that investigates the gene expression profiling of specimens with TP5, as a proxy of early tumor de-differentiation. We were able to elucidate unique genomic features in case of presence of TP5. We will try to implement these findings in our ongoing studies; we expect to implement a new predictive tool using tissue biopsy. This information has potential clinical applications during patient counseling regarding an individual’s risk of harboring a worse cancer phenotype and/or developing metastasis during post-operative follow-up.

Abstracts from Mount Sinai at Annual Meeting of the American Association for Cancer Research (AACR)

EDUCATION

PhD Clinical Encounter PhD candidates with a Cancer Biology concentration in the Graduate School of Biomedical Sciences have a unique opportunity to gain exposure to clinical care. Current students and principal investigators share their insights.

How I Became an Oncologist, Palliative Medicine... Cardinale B. Smith, MD, PhD, is an associate professor of medicine and the director of quality for cancer services at Mount Sinai Health System, in the Division of Hematology/Medical Oncology and Brookdale Department of Geriatrics and Palliative... Read more connection.asco.org

SERVING PATIENTS IN THEIR COMMUNITY

Cancer Physicians on Long Island Through Mount Sinai’s ever-expanding Cancer Network , specialists in Hematology and Medical Oncology are available to treat patients in their Long Island communities. Key individuals for patient referrals include:   Richard Lee, MD Interim Chief Hematology/Oncology Karine Austin, Administrator 516-536-1455 South Nassau Communities Hospital, Cancer Treatment and Care     Joshua Harris, MD Sarah Curtis, Administrator 631-628-5000 Mount Sinai Doctors Long Island, Hematology/Oncology

EVENTS - SAVE THE DATES

Kidney Cancer and Kidney Health Fair in recognition of National Kidney Month Learn about Kidney Cancer and Robotic Kidney Cancer Surgery Wednesday, March 27 11 am-2 pm 1468 Madison Avenue, Guggenheim Pavilion Read more

Multiple Myeloma Program for Patients and Caregivers in recognition of Multiple Myeloma Awareness Month Presenter: Joshua Richter, MD Wednesday, March 27 3-4:30 pm 1470 Madison Avenue, Sixth Floor, Room 6-101 Contact: Yu Mee Song, LCSW Read more   Advance Care Planning Information Session in recognition of National Health Care Decisions Day Information about Health Care Directives Monday, April 15 Noon-1 pm 1470 Madison Avenue, Second Floor, Seminar Room B RSVP to Stephanie Diaz , 212-824-8558 National Cancer Survivors Day Sunday, June 2 Noon-2 pm The Mount Sinai Hospital Stern Auditorium and West Lobby RSVP to Kaitlin Goldgraben, LCSW, 212-824-8884 Read more   All About Gay Men and Prostate Cancer Wednesday, June 19 5:30-7:30 pm Mount Sinai Downtown Union Square RSVP to Darren Arthur, LCSW, OSW-C, 212-844-6292 Read more

MOUNT SINAI CANCER IN THE NEWS - CLICK HERE

Do you have news for the next issue of    TCI Connections   ?  Please send to  Janet.Aronson@mountsinai.org    and  Rhaisili.Rosario@mssm.edu Remember to share  breaking news  and  high impact news  that might be appropriate for media coverage with Marlene Naanes 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. Marlene.Naanes@mountsinai.org  , 929-237-5802

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TCI Connections     is a monthly publication of The Tisch Cancer Institute. Ramon Parsons, MD, PhD, TCI Director Co-editors: Janet Aronson and Rhaisili Rosario Past issues of    TCI Connections    are available on the TCI website.