June/July 2020
Message from TCI Director Dr. Ramon Parsons
There are so many members of our TCI community who have gone above and beyond during this unprecedented time of COVID-19 and attention to racial inequities, and who continue to help steer our path forward as we adapt to ever-evolving challenges. I could not be more proud of our collaborative, and, yes, heroic efforts to ensure that patients receive the outstanding care that is a hallmark of our cancer program in a safe environment, and to move forward the research that supports development of new, effective therapies for all patients.

It is always difficult to single out one individual, but I would like to recognize a colleague who exemplifies extraordinary leadership on both COVID-19 and racial diversity fronts: Cardinale Smith, MD, PhD , Chief Quality Officer for Cancer for the Mount Sinai Health System.

When coronavirus hit, Dr. Smith stepped up to the plate with informed guidance, resolve, compassion, and a reassuring and inspiring presence, and she never lost a beat. She was instrumental in developing thoughtful safety procedures for cancer patients and staff, she kept everyone informed along the way, and she maintained a steady hand that was a beacon of comfort and hope.

Jenny Waltzer, Senior Director of Oncology Administration at The Mount Sinai Hospital, sums up what Dr. Smith has meant to the Ruttenberg Treatment Center staff in this Story of Strength: A Source of Truth and Strength at the Helm :
“[Dr. Smith] is one of the strongest leaders I have had the pleasure of working with during this time…Dr. Smith has shown what it truly means to be a leader during a crisis. Throughout the past few months…Dr. Smith always presented as calm and collected…Even if she was not delivering news we wanted to hear, we always knew it was accurate and real…Dr. Smith is always, and I mean always, available for questions or clarification, even questions of the smallest of nature…Dr. Smith, you made each day just a little easier…”
All of us a TCI echo Ms. Walter’s praise and extend our thanks to Dr. Smith.

In an equally important vein, Dr. Smith provides researched information, history, and perspective on diversity and racism, challenging all of us to examine our thought processes and biases, conscious or not, that influence our behavior with patients, co-workers, and everyone we encounter in our daily lives.

I encourage you to watch Dr. Smith’s June 18 webcast presentation: “ Health Care Disparities Unmasked: History and Hope ,” with an introduction on the MSHS Task Force to address racism by Gary Butts, MD , Chief Diversity and Inclusion Officer for the Mount Sinai Health System, and Senior Associate Dean for Diversity Programs, Policy and Community Affairs for the Icahn School of Medicine at Mount Sinai. Dr. Smith presents compelling examples of and data on the racial and ethnic disparities that have long existed in healthcare and strategies for improvement. She reminds us to uphold our mission of providing excellent, equitable cancer care to every patient, to work on overcoming barriers that prevent patients from seeking and/or receiving needed care, and to foster inclusiveness throughout the Health System.

As providers of cancer care and as cancer researchers, we have tremendous opportunity and responsibility to be aware and to act. Together, we can follow Dr. Smith’s lead and make a difference.
TCI Culture Survey 2020

In partnership with the Office for Diversity and Inclusion we invite you to complete the TCI Culture Survey 2020. This anonymous survey will assist with identifying opportunities and strategies to further advance our mission.

Completing this anonymous survey is optional. We encourage candid opinions and suggestions in the comment boxes.

Thank You,

Pershing Square Foundation Awards
The Pershing Square Foundation has awarded $3 million to nineteen recipients at ten academic research institutions conducting research related to the SARS-CoV-2 virus, including three recipients at Mount Sinai.
Nina Bhardwaj, MD, PhD – “Deconvolution of SARS-Cov2-specific immune responses in COVID-19 patients for broadly effective vaccines”  
Eirini Papapetrou, MD, PhD – “Genetic determinants of COVID-19 disease severity” 
Liam Holt, PhD, New York University, and Arvin Dar, PhD – “A synthetic viral-like-particle vaccine against SARS-CoV-2”
NIH Program Project Grant
The National Institute of Health has awarded Javier Bravo-Cordero, PhD , and his team funding to develop high-resolution, image-based studies to examine the cellular and subcellular changes in autophagy dynamics during aging and aging related diseases. This project is part of a Program Project Grant for which Ana Maria Cuervo, MD, PhD, at Albert Einstein College of Medicine (Einstein) is principal investigator; participating institutions are Einstein, Weill Cornell Medicine, and Mount Sinai. The project will utilize several autophagy mouse models, including a new reporter mouse model developed by Dr. Bravo-Cordero and colleagues (see recent article in Nature Communications ). This reporter mouse model will allow the Bravo-Cordero team to monitor changes in Chaperone Mediated Autophagy (CMA) during aging in vivo. They will study how restoration of CMA impacts aging and cognitive function in mice by analyzing at the single cell levels the activation of autophagy pathways.
Melanoma Research Alliance Team Service Award
Julio Aguirre-Ghiso, PhD , and Ashanai Weeraratna, PhD , at Johns Hopkins University Bloomberg School of Public Health, are co- principal investigators on a Melanoma Research Alliance Team Science Award , “The effects of age on tumor dormancy.” The award is collaboratively funded by Johns Hopkins University and Icahn School of Medicine at Mount Sinai. Hypothesizing that normal changes in both the immune system and other normal cells that occur during aging awaken dormant tumors, the researchers will investigate the processes that drive the emergence from tumor dormancy and how to target those processes in order to achieve durable therapy for cutaneous melanoma.
Leukemia Research Foundation
Bridget Marcellino, MD, PhD has been awarded a grant from the Leukemia Research Foundation for “Enhancing natural killer cell recognition of leukemic cells.” This translational project will be performed in collaboration with Lucas Ferrari de Andrade, PhD . The goals are to evaluate the efficacy and understand the mechanisms of a novel NK cell enhancing immunotherapeutic in a patient-derived xenograft model of acute myeloid leukemia.
Conquer Cancer Young Investigator Award
Deborah Marshall, MD, MAS, Resident/Research Fellow, Department of Radiation Oncology, received a Young Investigator Award from Conquer Cancer , the foundation of the American Society of Clinical Oncology, for “A multidisciplinary approach to preventing sexual dysfunction in women receiving pelvic radiation.”
NCI R21 - Developing a Therapeutic Platform for Adenoid Cystic Carcinoma
Marshall Posner, MD , and Ross Cagan, PhD , formerly at Mount Sinai and now at the Institute of Cancer Sciences, University of Glasgow, have been awarded an R21 grant from the National Cancer Institute for “Developing a Therapeutics Platform for Adenoid Cystic Carcinoma (ACC).” The funded research project involves sequencing the genetic composition of tumor and normal tissues from a series of patients with ACC, establishing a model in drosophila flies, studying the biology of the tumors, and screening drugs and drug cocktails for activity in the models.
ACC is a rare salivary gland tumor that has a slowly progressive course in many patients and for which there is no known effective therapy when the cancer recurs or metastasizes. There are currently no established tumor models in cell lines although tumors can be grown in immunodeficient mice, and research on the biology and treatment of ACC has been very limited.

Melanoma Research Alliance Pilot Awards
The Melanoma Research Alliance (MRA) has granted Hess Foundation – MRA Pilot Awards to Emily Bernstein, PhD , and Poulikos Poulikakos, PhD , for “Histone variant regulation of the melanoma immune microenvironment” and “Uncovering nodes of convergence of targeted and immune therapy in melanoma,” respectively.
MRA research awards support innovative ideas having the potential to rapidly improve outcomes for patients with melanoma. 
Request for Proposals

Application Deadline: September 24, 2020
The Young Investigator Award provides funding to promising investigators to encourage and promote quality research in clinical oncology. The purpose of this grant is to fund physicians during the transition from a fellowship program to a faculty appointment. 
Dissecting the Pol II transcription cycle and derailing cancer
with CDK inhibitors

This review article addresses the molecular mechanisms by which specific cyclin-dependent kinases (CDKs) are thought to act at discrete steps in the transcription cycle. The authors emphasize recent advances in understanding the transcriptional CDK network that were facilitated by development of small-molecule inhibitors with increased selectivity for individual CDKs. Disrupting the transcriptional CDK network with small molecules has the potential to disrupt signaling that is essential for survival of cancer cells and that can be leveraged for drug discovery efforts.  
The current paradigm and challenges ahead for the dormancy of disseminated tumor cells
Julio Aguirre-Ghiso, PhD , and colleagues from Université de Lyon

This paper reviews recent data on disseminated tumor cells that have furthered the understanding of cancer dormancy and discusses how this is leading to new strategies for monitoring and targeting dormant cancer. The authors focus mainly on in vivo and human data and how they inform evolving concepts about tumor dormancy, including the active role of the microenvironment.
Acute myeloid leukemia iPSCs reveal a role for RUNX1 in the maintenance of human leukemia stem cells

The researchers report that genetically clonal induced pluripotent stem cells (iPSCs) derived from an acute myeloid leukemia (AML) patient and characterized by exceptionally high engraftment potential give rise, upon hematopoietic differentiation, to a phenotypic hierarchy. They identify a cell fraction (iLSC) that can be easily isolated prospectively and that fulfills the hallmark features of leukemia stem cells (LSCs). Through integrative genomic studies of the iLSC transcriptome and chromatin landscape, they derive an LSC gene signature that predicts patient survival and uncovers a dependency of LSCs on the RUNX1 transcription factor. These findings can empower efforts to therapeutically target AML LSCs.
Comparative effects of oncogenic mutations G12C, G12V, G13D, and Q61H on local conformations and dynamics of K-Ras

Building on previous studies of the mechanisms by which oncogenic G12D mutation alters wild-type K-Ras conformations and dynamics, the researchers investigated whether the changes in nucleotide-bond K-Ras conformation and dynamics also show mutant-specific behavior. They investigated the changes in the conformational and dynamic behavior of active and inactive K-Ras caused by its most frequently observed oncogenic mutants other than G12D and analyzed the dynamics of each mutant protein in depth. Their findings on differences in local dynamics can further the understanding of the mechanisms that underlie biological differences between K-Ras mutants and inform targeted drug design.
ProNetView-ccRCC: a web-based portal to interactively explore clear cell renal cell carcinoma proteogenomics networks

While the NCI’s Clinical Proteomics Tumor Analysis Consortium (CPTAC) has been performing comprehensive large-scale proteogenomic characterizations of multiple cancer types for better understanding of the molecular basis of cancer, it is challenging to effectively visualize and navigate CPTAC-derived network models. In this paper, the researchers report on ProNetView-ccRCC, a web-based network exploration portal they developed for investigating phosphopeptide co-expression based on clear cell renal cell carcinoma (ccRCC) phosphoproteomics data. The tool enables users to query for association between abundance of each phosphopeptide in the network and clinical variables such as tumor grade. The portal is an open‐access freely available resource at  http://ccrcc.cptac-network-view.org/ .
Ancestry-specific predisposing germline variants in cancer
Oak N; Cherniack AD; Mashl RJ; TCGA Analysis Network;   Fred Hirsch, MD, PhD ;  Ding L; Beroukhim ; Zeynep H Gümüş, PhD ;  Plon SE; Kuan-Lin Huang, PhD

This paper reports on analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas
from a cohort of 9899 cancer cases to inform cancer genetic risk and prognosis of diverse populations. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPGs), the researchers analyzed the association between CPGs and cancer types within ancestral groups. While several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific. Studies using larger cohorts of diverse ancestries will be required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies.
A tertiary center experience of multiple myeloma patients with COVID-19: lessons earned and the path forward

This study of patients treated for myeloma provides a detailed analysis of a cohort of 58 myeloma and smoldering myeloma patients who developed COVID-19. Several demographic factors and comorbidities increased the risk of hospitalization and mortality, but myeloma therapy and immunoparesis did not influence outcomes. Survival was comparable to the overall population of New York during the pandemic, and patients generally mounted a significant antibody response to SARS-CoV-2. The data supports the need to maintain proactive management of myeloma patients, balancing the need for treatment with the increased risks in a subset of myeloma patients with COVID-19.
Trial design and endpoints in hepatocellular carcinoma: AASLD consensus conference

This review covers the full spectrum of hepatocellular carcinoma (HCC), from surveillance/chemoprevention to neoadjuvant and adjuvant trials after curative therapies and trials in intermediate and advanced stages of disease. It addresses the prospects for incorporating biomarkers and liquid biopsy into conventional clinical trials and the need for obtaining tissue and blood samples in all investigations. It also provides novel recommendations—from the American Association for the Study of Liver Diseases Consensus Conference—on trial design and endpoints in HCC with the goal of improving patient outcomes.  
Rigosertib in combination with azacitidine in patients with myelodysplastic syndromes or acute myeloid leukemia: results of a Phase 1 study
et al.

This paper reports the Phase 1 results from a Phase 1/2 study of patients with myelodysplastic syndromes, acute myeloid leukemia, and chronic myelomonocytic leukemia who had failed treatment with a hypomethylating agent. The addition of oral rigosertib to standard azacitidine resulted in a safety profile similar to standard dose single-agent azacitidine. The doublet therapy regimen produced an overall response rate of 56 percent. The findings support further clinical development of the novel sequential combination of oral rigosertib and standard dose azacitidine in patients with myeloid malignancies.
Impact of COVID-19 on prostate cancer management: guidelines
for urologists

This paper reports that prostate cancer patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started. Surgery or radiation therapy can be considered to limit any negative impact on prostate cancer outcomes.
TCI presentations and presenting authors can be found here.
During the peak of the COVID-19 pandemic, our cancer clinical trials program went into a holding pattern in order to focus efforts on treatment options for COVID-19 patients and to minimize exposure for our cancer patients. Now that patient care services have resumed normal operations, we are once again enrolling patients on cancer clinical trials as appropriate in order to provide the most advanced care for optimal outcomes.

To search for a cancer clinical trial, go to our “Find a Clinical Trial” page on the TCI website and search by disease/cancer type, principal investigator, and/or trial phase. Alternatively, you can contact our Cancer Clinical Trials Office at 212-824-7209 or [email protected] for assistance.

If you have questions, please contact Karyn Goodman, MD, MS , Associate Director of Clinical Research for TCI, at [email protected] or Lisa Gaynes, CCRP, Executive Director of Clinical Research Administration, at [email protected] . For information about early phase trials, please contact our Early Phase Trial Unit , u nder the leadership of   Matthew Galsky, MD , at [email protected] .
Sirish Dharmapuri, MD, Hematology and Medical Oncology
Sirish Dharmapuri, MD, has joined the faculty as Assistant Professor of Medicine (Hematology and Medical Oncology) with a focus on solid tumors, particularly gastro-intestinal cancers. Dr. Dharmapuri will see patients at Mount Sinai West and Ruttenberg Treatment Center at The Mount Sinai Hospital campus, and will also develop and participate in clinical research. Dr. Dharmapuri completed fellowship training in Hematology and Medical Oncology at Icahn School of Medicine at Mount Sinai and Internal Medicine residency at Scranton Temple Residency Program (now known as The Wright Center for Graduate Medical Education) /Veteran Affairs Medical Center. He earned his medical degree from Vydehi Institute of Medical Sciences in Bangalore, India, and practiced as a primary care physician in India for two years prior to residency training. Dr. Dharmapuri is an ad hoc reviewer for the Journal of Gastrointestinal Oncology .
Leonard Naymagon, MD, Hematology and Medical Oncology
Leonard Naymagon, MD , has joined the faculty as Assistant Professor of Medicine (Hematology and Medical Oncology). He will see patients at Ruttenberg Treatment Center at The Mount Sinai Hospital campus and at Mount Sinai Downtown with a focus on benign hematology, and will develop and participate in related clinical research. Dr. Naymagon completed his fellowship in Medical Hematology and Oncology at Icahn School of Medicine at Mount Sinai and residency in Internal Medicine at New York University School of Medicine. He earned his medical degree from Albert Einstein College of Medicine. Dr. Naymagon has worked with John Mascarenhas, MD , on development of research databases for hemophagocytic lymphohystiocytosis, portal vein thrombosis, and acute promyelocytic leukemia.
Save the Date: Frontiers In Oncology Seminar Series
Tuesday, September 15, 12 noon
Guest presenter: David Tuveson, MD, PhD

Dr. Tuveson is a world-renowned physician-scientist whose basic and translational research focuses on the biology of pancreatic cancer and on identifying and testing in preclinical and clinical settings new approaches for diagnosing and treating the disease. He is the director of the Cold Spring Harbor Laboratory Cancer Center and chief scientist for the Lustgarten Foundation , the largest private funder of pancreatic cancer research. Dr. Tuveson is president-elect of the American Association for Cancer Research (AACR) and scientific editor of the AACR journal Cancer Discovery .
Lung Cancer Risk
Zeynep H. Gümüş, PhD , presented "Inherited genetic variants in lung cancer risk" at the May 12 Computational Cancer Genomics Working Group Evening Lecture , New York Genome Center.
Protogenomic Data Analysis
Dr. Gümüş also presented on April 9 at a NCI Office of Cancer Clinical Proteomics Research webinar on the Network Exploration Tool, designed by Mount Sinai’s Protogenomic Data Analysis Center team to explore novel interactions in the context of a specific cancer type. 
First diagnosed a decade ago, Tanya Bhatia now has stage 4 breast cancer and has had to continue with chemotherapy during the coronavirus pandemic. She says she feels safe coming in for her care.
May 14

Discussion with cancer clinicians and researchers about TCI’s efforts to combat COVID-19 on the frontlines and in our laboratories

Faculty Participants:

June 11

For patients, emphasizing resumption and scope of cancer care services and safety measures

Faculty Participants:

June 25

Faculty Participants:
Do you have news for the next issue of  TCI Connections

 Please send to  Janet Aronson and Rhaisili Rosario

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
Co-editors: Janet Aronson and Rhaisili Rosario
Past issues of    TCI Connections   are available on the TCI website