September 2020
Message from TCI Director Dr. Ramon Parsons
NCI Cancer Center Support Grant Renewal
I am delighted to report that The Tisch Cancer Institute (TCI) has successfully renewed its NCI Cancer Center Support grant for a period of five years, extending important funding and NCI-designated cancer center status, first awarded to TCI in 2015. This competitive renewal is a testament to our robust programs that support our mission of advancing basic, clinical and population health cancer research, in order to prevent cancer in healthy individuals and improve the lives of cancer patients and their families in our diverse communities.

Our four research programs comprising the grant are:
  • Cancer Immunology—identifying the mechanisms underlying the suppression of anti-tumor immunity in order to inform development of effective immunotherapies
  • Cancer Mechanisms— understanding the biology of cancer cell development and proliferation, and identifying candidate therapeutics that target biological pathways
  • Cancer Prevention and Control—reducing the burden of cancer incidence, mortality, and disparities in cancer risks and outcomes
  • Cancer Clinical Investigation – developing new treatment approaches to cancer by translating discoveries into therapeutic trials

Also supported by the grant are our five shared core resources—Flow Cytometry, Mouse Genetics, Microscopy, Biostatistics, and the Human Immune Monitoring Center—and additional resources in development related to tissue biorepositories, bioinformatics, and analysis of biomedical data.

The work that went into preparing the Cancer Center Support grant application was monumental. Our successful renewal reflects the collaborative efforts of all involved and institutional commitment from Mount Sinai. We are also indebted to our External Advisory Board for insightful guidance.

We look forward to the next five years of innovation and discovery that advance the course of treatment and survival for cancer patients. 
Additional Good News: The Mount Sinai Hospital was ranked among the top 50 adult cancer hospitals for 2020-21 by U.S. News.
Deirdre J. Cohen, MD, has joined Mount Sinai as Associate Professor of Medicine (Hematology and Medical Oncology) and Director of the Gastrointestinal (GI) Oncology Program for the Health System. She is also Medical Director of the Cancer Clinical Trials Office at The Tisch Cancer Institute. Dr. Cohen has expertise in pancreatic and other GI cancers and has been awarded extensive grant funding for research in these malignancies. She is an accomplished clinical trialist, focused on the development of immune targeted strategies and biomarker-driven studies with translational endpoints. She serves as principal investigator on numerous clinical trials pertaining to novel therapeutic approaches for patients with GI malignancies.
“We are delighted to be welcoming Dr. Cohen to The Tisch Cancer Institute. Dr. Cohen’s arrival is the result of a national search for a talented leader of GI medical oncology who is committed to clinical research,” said Dr. Ramon Parsons, TCI Director.
Dr. Cohen received her MD from SUNY Health Science Center at Brooklyn and a Master of Science degree in Clinical Investigation from New York University (NYU). She completed residency in Internal Medicine at New York-Presbyterian/Weill Cornell Medical Center, and fellowship in Hematology/Oncology at NYU Langone School of Medicine. She is board certified in Internal Medicine, Medical Oncology, and Hematology. Prior to joining Mount Sinai, Dr. Cohen was on the faculty in the Division of Medical Oncology at NYU for 13 years. She recently served as Medical Director for the Perlmutter Cancer Center Clinical Trials Office and Acting Director of NYU GI Medical Oncology.
“We are looking forward to welcoming Dr. Cohen as she brings her extensive knowledge and expertise to developing cutting-edge therapeutic approaches to GI cancers at Mount Sinai,” said Dr. William Oh, TCI Deputy Director and Chief of the Division of Hematology and Medical Oncology.
Dr. Cohen sees patients at The Ruttenberg Treatment Center and Mount Sinai West.
Deborah Doroshow, MD, PhD, has been appointed Associate Program Director for Research and Career Development for the Hematology and Medical Oncology fellowship program. Working with Adriana Malone, MD, and Peter Kozuch, MD, Dr. Doroshow will conduct individualized mentoring with fellows, develop a research curriculum for the fellows with specific courses in clinical trial design and grant writing, and develop an infrastructure for regular assessment of their research plans and progress.
Sacha Gnjatic, PhD, together with Jean-Frédéric Colombel, MD, and Jeremiah Faith, PhD, have been awarded a U01 grant (Research Project Cooperative Agreement) for “Characterizing and predicting colitis in immune checkpoint blockade-treated cancer patients,” with funding split between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the NCI. Philip Friedlander, MD, PhD; Madhu Mazumdar,PhD; and David Faleck, MD, and Jedd Wolchok, MD, PhD, at Memorial Sloan Kettering Cancer Center are also participating.
David Domiguez-Sola, MD, PhD, has received grant funding from St. Baldrick’s Foundation to study the mechanisms of disease in Burkitt lymphoma—an aggressive form of childhood lymphoma with few treatment options—and identify therapeutic strategies that are more effective and less toxic than those currently in use.
Miriam Merad, MD, PhD, and Ido Amit, PhD, with the Department of Immunology at the Weizmann Institute of Science, have received the Max Ritvo, Alan Slifka and Desiree Dato Award for Fusion-Oncoprotein Cancers and Metastasis. They will explore how to alter the immune system in order to prevent metastasis. The award is funded collaboratively by the Alan B. Slifka Foundation, the Israel Cancer Research Fund, and the Samuel Waxman Cancer Research Foundation.
Joshua Brody, MD, is one of five recipients of the Lloyd J. Old STAR (Scientists Taking Risks) Awards for exploration of out-of-the-box research in cancer immunology from the Cancer Research InstituteDr. Brody is refining in situ vaccination, an approach that has the potential to teach a patient’s immune system to recognize tumor cells and target them throughout the body.

Bachir Taouli, MD, and colleagues were awarded R01 funding from the NCI for a prospective, multicenter single arm, non-randomized study to assess the performance of abbreviated MRI (AMRI) using gadoxetate as a screening modality for early detection of hepatocellular carcinoma (HCC) in 820 patients with cirrhosis. AMRI will be compared to ultrasound for HCC detection. The incremental value of circulating tumor DNA will be assessed. The four centers are the Icahn School of Medicine at Mount Sinai (coordinating center), the University of California San Diego, the University of Wisconsin-Madison, and Duke University. Dr. Taouli serves as the contact PI for the study.
Julio Aguirre-Ghiso, PhD, has been awarded RO1 grant funding from the NCI for “Mechanisms of uveal melanoma dormancy and targeted therapy tolerance.” Andrew Alpin, PhD, at Thomas Jefferson University, is Co-PI on this collaborative project. The study aims to determine how dormancy and oncogenic signaling pathways dictate survival and quiescence of uveal melanoma disseminated tumor cells and how to target them to prevent metastatic re-growth. The goal is to develop new treatment options that result in more durable therapy responses.
Samir Parekh, MD, and Michael Wang, MD, (MD Anderson) have been awarded a multi-PI R01 grant from the NCI for “Targeting SOX11 in mantle cell lymphoma.” This study aims to expand the understanding of mantle cell lymphoma (MCL) pathogenesis to identify new targets and therapeutic options. The researchers will use a mouse model they developed to define the mechanism by which the SOX11 transcription factor increases B-cell receptor signaling in MCL and determine the mechanisms by which SOX11 cooperates with Cyclin D1 (CCND1) to drive MCL. The therapeutic advantages of inhibiting SOX11 may be substantial, as the majority of MCL patients relapse after immune-chemotherapy and have a poor prognosis despite novel targeted therapeutics such as BTKi and BCL2i. 
Jose Javier Bravo-Cordero, PhD, has received funding from the Adenoid Cystic Carcinoma Research Foundation (ACCRF) to study progression and metastasis of adenoid cystic carcinoma by using in vivo models and high resolution imaging. This builds on his research—“ACC in vivo model system"—previously funded by the ACCRF.
Melanoma Res Alliance
The Melanoma Research Alliance welcomes proposals for pre-clinical, translational, and early clinical research. Special opportunities include young investigator awards in pediatric melanoma, radiation oncology, and immunotherapy.
Due date: November 4
Questions? Contact Honour Harlowe with Mount Sinai's Corporate and Foundation Relations team.
The DeGregorio Family Foundation for Gastric and Esophageal Cancer is accepting applications for research on gastroesophageal malignancies.
Due date: November 3

The application period for the Pershing Square Sohn Prize for Young Investigators opens on October 5.
Due date for Letter of Intent: November 9
JCO Cover
Journal of Clinical Oncology. 27 Jul 2020. PMID: 32716739

Advanced hepatocellular carcinoma (HCC) is associated with poor prognosis, despite recent advances in treatment. This paper reports on a phase 1b single-arm study with patients treated in the first-line setting with lenvatinib plus pembrolizumab. Response rates indicate that multikinase inhibition with lenvatinib plus PD-1 inhibition with pembrolizumab yields improved antitumor activity. Based on data from this study, the FDA granted a breakthrough therapy designation for the combination of lenvatinib and pembrolizumab for the treatment of patients with newly diagnosed, advanced, unresectable HCC that is not amenable to locoregional treatment. Dr. Llovet was the most senior investigator of this multi-center study. 

Nature Structural & Molecular Biology. 17 Aug 2020. PMID: 32807989

This paper reports on research that has unraveled for the first time the three-dimensional structure and mechanism of a complex enzyme—DNA polymerase ζ (Polζ)—that protects cells from constant DNA damage. The researchers used advanced cryo-electron microscopy to gain insights into the pentameric ring-like architecture of Polζ at near-atomic resolution and identify structural elements that allow Polζ to synthesize DNA and perform translesion synthesis. The structures provide an unprecedented framework for the development of therapeutics to treat chemotherapy-resistant cancers.

JCO Oncology Practice. 4 Aug 2020. PMID: 32749930

Goals-of-care (GoC) discussions enable physicians to tailor treatments to their patients’ unique values and goals. Many physicians typically feel these discussions take a long time and may be less likely to talk with patients about their goals of care. This paper reports that GoC discussions take less time than expected by physicians; the median encounter time was 15 minutes as measured by visit encounter time with oncologists from community, academic, municipal, and rural hospitals treating patients with advanced cancer. 

Breast Cancer Research. 29 Jun 2020. PMID: 32600444

Protein kinase C theta (PRKCQ/PKCθ) is a serine/threonine kinase that is highly expressed in a subset of triple-negative breast cancers (TNBC) and promotes their growth. The researchers identified a novel mechanism by which PRKCQ regulates the apoptotic response to chemotherapy, specifically by regulating levels of Bim, a pro-apoptotic Bcl2 family member that serves as a set point molecule for sensitivity to chemotherapy and targeted therapies. The data support the promising potential of PRKCQ inhibition as a therapeutic strategy to suppress TNBC tumor growth and survival in combination with standard-of-care chemotherapy.

Urologic Oncology. 11 Jul 2020. PMID: 32665122

While significant advancements in treating urothelial carcinoma of the bladder (UCB) have been made with the use of immunotherapeutics, only a small subset of patients with UCB benefit from these treatments. With a focus on the need for novel checkpoint molecules, the researchers demonstrate that UCB upregulates the inhibitory receptors TIM-3 (T-cell immunoglobulin domain and mucin domain-containing molecule) and TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) by natural killer and T cells in a tissue- and disease-stage-specific manner. Thus, TIM-3 and TIGIT are possible targets, as monotherapy or in combination with other immune checkpoint inhibitors.

Nature Communications. 2020 Aug 28. PMID: 32859893

Gene transcription by RNA polymerase II underlies cell proliferation or death, and is regulated by enzymes that add phosphates or remove them from components of the transcription machinery. In this paper, the researchers define two kinase-phosphatase switches that regulate different steps of the transcription cycle in human cancer cells. Their study shows for the first time that a key transcriptional kinase—Cdk9—acts in opposition to two different phosphatases—PP4 and PP1—at the entry to and exit from the elongation phase of the transcription cycle. 

British Journal of Haematology. 30 Jul 2020.

Daratumumab is a CD38‐targeting monoclonal antibody approved for intravenous (IV) infusion for multiple myeloma (MM). Recently, the FDA approved a subcutaneous formulation of dratumumab (DARA SC). This paper reports the efficacy and safety data from the Phase II PLEIADES multicenter study of DARA SC in combination with standard-of-care regimens for patients with newly diagnosed multiple myeloma and patients with relapsed/refractory multiple myeloma. DARA SC was found to be efficacious, generally safe and well tolerated, and had a lower infusion-related reaction incidence compared to combination therapies with daratumumab IV. DARA SC allows for a shorter administration time, reducing the treatment burden for patients. Results support the use of DARA SC in combination with standard treatment regimens.

Leukemia & Lymphoma. Sep 2020. PMID: 32812822

This paper reports on the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide, and weekly dexamethasone (PCD) in patients with relapsed/refractory multiple myeloma who were refractory to lenalidomide. Overall response rate was 73 percent, median progression free survival was 13.3 months, and median overall survival was 57.2 months. The study confirms the efficacy of PCD, identifies MYC as a biomarker for inferior outcome, and sheds light on how this drug combination alters the immune phenotype in the tumor microenvironment as well as in the blood. Progression free survival is amongst the highest published to date with an all oral, cost-effective regimen that is not significantly impacted by renal impairment.

Annals of Epidemiology. Aug 2020. PMID: 32620423

This study was designed to examine variation in multiple myeloma (MM) incidence and mortality rates by race-ethnicity and geographic location and evaluate their correlation with neighborhood-level population covariates within New York City (NYC). Findings showed that NYC neighborhoods with large minority populations have higher prevalence of poverty-related factors associated with MM incidence and mortality, warranting public health policies to address exposures and access to care.

CA: A Cancer Journal for Clinicians. 07 Aug 2020. PMID: 32767764

The authors review the history of muscle‐invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe major advances in treatment, and offer future directions for therapeutic development. Although cisplatin‐based chemotherapy remains the standard therapy in the perioperative and first‐line metastatic settings for urothelial cancer, novel therapies are rapidly altering treatment paradigms. This includes the approvals of five immune checkpoint inhibitors in the platinum‐refractory setting and of two in the first‐line setting for patients who are cisplatin‐ineligible and harbor tumors with high PD‐L1 expression. Future directions will include a focus on moving novel therapies into earlier disease stages, optimizing sequencing and combinations of therapies, and identifying novel therapeutic targets.
From the laboratory of Amaia Lujambio, PhD, et al.

Gastroenterology. 16 Aug 2020. PMID: 32814112

This paper reports on the development of novel mouse models of hepatocellular carcinoma (HCC), each one harboring genetic alterations in two driver genes, capturing the human HCC diversity that partially explains the low efficacy of available therapies. The researchers generated murine cell lines derived from the mouse models and used them to identify targeted therapies that can be validated in vivo. They demonstrated that different combinations of genetic alterations can contribute to HCC formation and progression. The models represent a unique resource that is available for the scientific community to generate and test hypotheses, dissect the mechanisms underlying cooperation between different driver genes and inter-tumor heterogeneity, and test personalized therapies. 
Uroosa Ibrahim, MD, Hematology and Medical Oncology
Uroosa Ibrahim, MD, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology). She sees patients at The Ruttenberg Treatment Center, with a clinical focus on hematological malignancies, bone marrow transplantation, CAR-T cell therapy and other novel cellular therapies. Dr. Ibrahim earned her medical degree from Ziauddin Medical University in Karachi, Pakistan. She completed residency in Internal Medicine and fellowship in Hematology and Oncology at Northwell Health Staten Island University Hospital where she also served as Chief Fellow. Dr. Ibrahim completed advanced fellowship training in Bone Marrow Transplantation and Cellular Therapy at Mount Sinai. Dr. Ibrahim is board certified in Internal Medicine, Hematology, and Medical Oncology. Among her recent publications is a report, co-authored by Keren Osman, MD, on cytopenias following CAR T-cell therapy in Biology of Blood and Marrow Transplantation.
Vaibhav Patel, MD, Hematology and Medical Oncology
Vaibhav Patel, MD, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology). He sees patients at The Ruttenberg Treatment Center and Mount Sinai West, with a focus on genitourinary malignancies. He is also Assistant Director of Cancer Clinical Trials at Mount Sinai West. Dr. Patel completed his fellowship in Hematology and Medical Oncology at Mount Sinai, serving as Chief Fellow in his final year. He completed residency training in Internal Medicine, also at Mount Sinai, and earned his medical degree from the Feinberg School of Medicine at Northwestern University. His research interests include development of novel therapeutics, particularly immune-based therapies, in genitourinary malignancies, and precision oncology in prostate cancer. Dr. Patel has numerous first-author publications in peer-reviewed journals such as CA: A Cancer Journal for Clinicians, Annals of Oncology, Nature Reviews Urology, and European Urology
House Staff
The Division of Hematology and Medical Oncology welcomed seven
first-year fellows in July. The fellows and their Internal Medicine residency programs:
  • Bailey Fitzgerald, MD, Yale
  • Melanie Kier, MD, University of Pennsylvania
  • Hannah Levavi, MD, Mount Sinai
  • Rima Patel, MD, Tufts
  • Sridevi Rajeeve, MD, Mount Sinai West/Morningside
  • Andrew Srisuwananukorn, MD, University of Illinois
  • Linda Wu, MD, Weill Cornell 

Also, Jacques Azzi, MD, came on board as an advanced fellow in Bone Marrow Transplantation and Cellular Therapy for 2020-2021. Dr. Azzi earned his MD at the University of Balamand Medical School in Lebanon. He completed his Internal Medicine residency at Staten Island University Hospital and Hematology/Oncology fellowship at NYU Langone Health.
High School Students
TCI hosted ten Black and Latino male students—rising seniors at the Manhattan Center for Science and Mathematics—the week of July 20 for the Lloyd Sherman Scholars Program. The curriculum, organized by Janice Gabrilove, MD, included presentations on cancer biology, radiation oncology, tumor metastasis, epigenetics, cancer drug/immunotherapeutic discovery, and more, and a virtual lab tour. Participating faculty and staff: Drs. Janice Gabrilove, Richard Bakst, Javier Bravo-Cordero, Deanna Benson, Emily Bernstein, Dan Filipescu, Sina Jostes, Dan Hasson, Thomas Wolken, Umet Ozbek; and Maria Dimopoulos, MBA, RT (T).
Patient Shahonna Anderson managed a cancer diagnosis, surgery, radiation, and chemotherapy at the height of COVID-19.
She tells her story on Mount Sinai’s Road to Resilience podcast.
Service of Remembrance honoring and celebrating cancer patients
Two dates: September 23 at 6 pm and October 6 at noon
Passcode: 264044
Phone: 929-436-2866, ID: 976-5310-7621
Three members of The Tisch Cancer Institute will be honored at the Jacobi Medallion Award Ceremony, to be streamed online on October 6.

Recorded Webinars
Password: ISMMS
Faculty Participants: Drs. Ramon Parsons, Gary Butts, Cardinale Smith, Emanuela Taioli, Emily Gallaher, Hannah Irie

Update on frontline therapy, relapsed/refractory myeloma, CAR T-cell therapy, novel therapies
Faculty Participants: Drs. Ajai Chari, Deepu Madduri, Shambavi Richard, Joshua Richter
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