April 2020
MESSAGE FROM DR. RAMON PARSONS
In late January, we started to receive Mount Sinai broadcast notifications about the 2019 novel coronavirus (2019-nCoV) outbreak. Since then, the pace of activity and influx of patients to our hospitals has been relentless. The inpatient census peaked the first week in April with more than 2,000 COVID-19 positive patients and patients under investigation. More than 450 patients were in intensive care units. Thankfully, the curve is now on a downward trajectory.
 
The response from our cancer professionals and staff at The Tisch Cancer Institute in the face of this challenging crisis has been remarkable. Our physicians have willingly redeployed to patient care units in need and have ensured safe practices in cancer units for COVID-19 positive patients and cancer units for uninfected patients. Our scientists have quickly turned their energies to investigating novel strategies to combat the virus. Our translational researchers have optimized the clinical trials process to launch COVID-19-focused studies. Our staff throughout the entire cancer enterprise have readily adapted to maximize our efficiency and effective collaboration. Whether on the frontline at the bedside or at the bench or remotely from home, everyone has demonstrated flexibility, dedication, ingenuity, and compassion. I could not be more proud and humbled.
 
We know that cancer does not take a break, no matter the circumstances, and that continuity of care for cancer patients is essential for optimal outcomes. As depicted on this graph, our clinicians have ramped up telemedicine visits to ensure that patients receive care in a timely fashion.
For those patients better served by on-site visits, we have continued cancer-related care while exercising safety measures. We are carefully planning for a more robust resumption of on-site cancer services, including cancer clinical trials, as the COVID-19 situation continues to improve.
 
As always, our top priority is to care for patients and develop treatment interventions and preventive measures that contribute to saving lives. Despite COVID-19, we are staying true to our mission. To all members of our TCI community, thank you for your ongoing commitment and professionalism. 

ADVANCEMENTS AGAINST COVID-19

Mount Sinai began administering remestemcel-L to patients with moderate to severe cases of COVID-19-related acute respiratory distress syndrome in late March under the Food and Drug Administration’s compassionate use program. Remestemcel-L has previously been tested in bone marrow transplant patients, who can experience an overactive immune response similar to that seen in severe cases of COVID-19.
 
“We are encouraged by what we have seen so far and look forward to participating in the randomized controlled trial starting soon that would better indicate whether this is an effective therapy for patients in severe respiratory distress from COVID-19,” said Keren Osman, MD .

Dr. Osman is the Medical Director of the Cellular Therapy Service in the Bone Marrow and Stem Cell Transplantation Program at TCI. 



Controlling Extreme Inflammation in Severe Cases of COVID-19
May Help Save Lives  

Under the leadership of  Miriam Merad, MD, PhD , Director of the Precision Immunology Institute and Co-Leader of the Cancer Immunology program, Mount Sinai has created a test that monitors a patient’s inflammatory response to COVID-19 and has helped launch a clinical trial using the drug sarilumab to manage these responses. 

“You need a strong immune response to fight the virus and this is why some people do well,” said Dr. Merad. “But others develop this storm of cytokines and this is what leads to fatalities. People are not dying from a virus that is running rampant in their bodies and killing tissue. We believe people are dying because of excessive inflammation. If we learn how to prevent this damaging immune response without compromising the fight against the virus we will be able to save many lives while waiting for curative treatment such as an antiviral drug or a vaccine.” 

GRANT AWARDS
R01 Award - Bladder Cancer
Co-Principal Investigators Nina Bhardwaj, MD, PhD , Matthew Galsky, MD , and
Jun Zhu, PhD, have been awarded an R01 grant from the National Cancer Institute for “Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer.” The research will investigate whether myeloid cells drive primary resistance to immune checkpoint inhibition (CPI) in bladder cancer. It will also explore whether comprehensive cellular and molecular maps of bladder cancer facilitate identification of precise monocyte-MΦ subpopulations and CAF-myeloid-T-cell interactions that can be leveraged to define novel biomarkers and therapeutic targets. The goal is to expand the benefits of CPI beyond the 15-20 percent of patients with bladder cancer that respond to treatment.
R01 Award - Regulating Ras in development
Cathie Pfleger, PhD , received R01 funding from the National Cancer Institute for “Regulation of Ras in development by post-translational modification.” Dr. Pfleger and her research team discovered that impairing Ras ubiquitination in vivo in Drosophila led to striking effects on cell proliferation, survival, developmental patterning, and organismal longevity, reflecting a role for Ras ubiquitination in development, tumor suppression, and survival. The goal of this funded research is to identify the Ras Tyrosine 4 kinase(s) and phosphatase(s) and to characterize their roles in regulating Ras in development. This could inform targeted therapies for cancer and other diseases.
Defeat Brain Tumors Grant Award
Adilia Hormigo, MD, PhD , received a Defeat Brain Tumors Grant Award from the National Brain Tumor Society . The aims of her research are to characterize mutations encoding neoantigens in adult and pediatric high-grade gliomas, and to generate a personalized multi-peptide vaccine based on the neoantigens of each patient’s tumor. Once the mutations are called they are ranked by immunogenicity, and the long synthetic peptides are synthesized and loaded to the patient’s own dendritic cells. Some of the patients will also receive immune checkpoint blockade. The goal is to reverse the immunosuppression of the tumor microenvironment of glioblastoma (GBM) and with this strategy successful treat GBM patients.
Training Grant in Clinical Oncology Social Work
Alison Snow, PhD, LCSW-R, OSW-C, has received a two-year renewal of her Master’s Training Grant in Clinical Oncology Social Work from the American Cancer Society . Dr. Snow is Assistant Professor of Environmental Medicine & Public Health and Director of Cancer Supportive Services, Mount Sinai Downtown. The grant provides funding for field training for a Master of Social Work graduate student. The goal is to provide an educational experience that helps solidify the student’s interest in oncology social work. 
GRANT OPPORTUNITIES
Stand Up To Cancer
Stand Up To Cancer (SU2C) Invites applications for the SU2C Health Equity Breakthrough Team Research Grant Program with a focus on new approaches to address health equity in the context of cancer research. Letter of intent due date: September 1, 2020


Memorial Sloan Kettering Lymphoma SPORE
  • 2020-2021 Developmental Research Program (DRP) Awards. Objective: to support pilot projects that explore innovative ideas in basic and translational research in lymphoma

  • 2020-2021 Career Enhancement Program (CEP) Awards. Objective: to identify, train and/or develop talented individuals to become successful translational investigators in the field of lymphoma

Investigators at Memorial Sloan Kettering Cancer Center, Rockefeller University, Weill Cornell Medical Center, Columbia University, Mount Sinai, and NYU are eligible. Proposal due date: July 1, 2020


The Mark Foundation for Cancer Research
The Mark Foundation for Cancer Research offers Emerging Leader Awards to support innovative research from the next generation of leaders in cancer research. These grants are awarded to outstanding early career investigators to support high-impact, high-risk projects that are distinct from their current research portfolio. 
Letter of intent due date: June 4, 2020


The Kidney Cancer Association
The Kidney Cancer Association invites applications for its Advanced Discovery Awards (ADAs) and Young Investigator Awards (YIAs). A total of $1.3 million in funding is available: two $500,000 ADAs and four $75,000 YIAs. Submission Information

  • Letter of intent due date for ADA awards: May 20

  • No letter of intent is required for YIA awards; full proposals will be accepted through August 5.
PUBLICATIONS
A conserved dendritic-cell regulatory program limits antitumour immunity


Findings reveal a targetable immmunoregulatory program—expressed by dendritic cells across different tissues, tumor types, and species—that restrains DC immunostimulatory function and controls the threshold of T-cell activation. The results extend prior work showing that the IL-4/IL-13 pathway can promote tumor growth and emphasize the need to test combination therapies that block both PD-L1 and IL-4 signaling in different cancer types.
Randomized double-blind Phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients with metastatic urothelial canc er


Metastatic urothelial cancer is a relatively chemotherapy-sensitive solid tumor. However, the vast majority of patients experience disease progression despite first-line platinum-based chemotherapy while on treatment, or within months of completing treatment, highlighting the need for better therapeutic strategies. This study found that earlier use of PD-1 blockade with pembrolizumab, at the time of cessation of first-line chemotherapy, leads to additional objective responses and significantly prolongs progression-free survival in patients with metastatic urothelial cancer. 
A reference profile-free deconvolution method to infer cancer cell-intrinsic subtypes and tumor-type-specific stromal profiles


This paper reports on a computational method, DeClust, for modeling bulk tumor tissue transcriptomic data that simultaneously delivers a reference profile-free deconvolution of bulk tumor gene expression data into cancer, immune, and stromal cellular compartments, as well as a cancer cell-intrinsic clustering of cancer samples to uncover molecular cancer subtypes. This may lead to mechanistic and clinical insights across multiple tumor types and help identify potential driver genes and associated therapeutic targets.


High-throughput cytostatic and cell death assays are a critical component of pharmacological screens and mechanism-based interrogations into cellular biology. The Chipuk Laboratory developed a method for single-cell and population-level analyses using real-time kinetic labeling (abbreviated "SPARKL") with non-toxic fluorescent probes and high-content live-cell imagers. The protocol can be broadly applied to most cell culture model systems to reveal and quantify a diversity of cell death mechanisms, including those most relevant to cancer biology and treatment.
COVID-19 infection in cancer patients: early observations and
unanswered questions


Dr. Oh comments on a retrospective cohort study of 28 cancer patients from three hospitals in Wuhan, China, Zhang, et al. that found that the patients were at high risk for severe events and mortality. Dr. Oh suggests that while caution is necessary in interpreting these findings, the study represents an important preliminary contribution to the understanding of the risk and effects of CVOID-19 infection in cancer patients. 
Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): a comparison of VRd, KRd, and IRd
Ajai Chari, MD , et al.


This paper reports on a retrospective, comparative analysis of time to next therapy (TTNT) in a representative cohort of patients with relapsed/refractory multiple myeloma in routine care with ixamobid, carfilzomib + lenaldomide/dexamethasone (Rd), or bortezomib + Rd in lines of therapy (LOT) 2 or greater. The proteasome inhibitor-Rd triplet combinations were comparable in TTNT among all patients treated on LOT 2 or greater. However, the results suggest a gap between the efficacy observed in clinical trials and a lower effectiveness in the real world, underlining the limited generalizability of results from randomized clinical trials where 50-75 percent of patients are excluded due to inability to meet eligibility criteria. Individualized treatment recommendations based on patient characteristics such as age and comorbidity may help improve real-world outcomes.
COVID-19 and bacillus Calmette-Guérin: what is the link?

 Manuscript draft

This editorial highlights information about the role of bacillus Calmette-Guérin (BCG) vaccination in the context of COVID-19. 
EDUCATION
The Tisch Cancer Institute Summer Scholars
Two students at the Icahn School of Medicine at Mount Sinai have been selected for the 2020 TCI Summer Scholars Program . Makda Zewde will work in the laboratory of James Ferrara, MD , and Ariana Mills will work in the laboratory of Hank Schmidt, MD, PhD . The program—for first year medical students who have not yet had extensive research experience—provides support for original cancer research under the tutelage of a TCI faculty mentor that will ideally lead to a scholarly research year between the student’s third and fourth years.
PRESENTATIONS
Cancer Prevention and Control Research Program

April 14
HPV

The Tisch Cancer Institute Seminar Series

April 14
The Exposome and Precision Medicine: Everything That Rises Must Converge


April 21
Molecular Monitoring of Liver Cancer: Impact of Heterogeneity and Role
of Liquid Biopsy - Augusto Villanueva, MD, PhD

Repurposing of Clinically Approved Drugs for Treatment of COVID-19 - Kris White, PhD

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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.