Updates to Mount Sinai's bladder cancer website and the multiple myeloma website reflect each program's new designation as a Center of Excellence at The Tisch Cancer Institute. This designation recognizes comprehensive excellence in clinical care and translational research, and trailblazing advancements that are changing the course of cancer treatment for improved quality of life and survival. Cancer Centers of Excellence feature multidisciplinary care, broad access to robust clinical trials and supportive care services, and a seamless experience for patients from screening through survivorship. They also provide outstanding training programs for future physicians and scientists.
The Center of Excellence for Bladder Cancer is under the leadership of co-directors Matthew Galsky, MD, and Peter Wiklund, MD, PhD. Sundar Jagannath, MBBS, is the director of the Center of Excellence for Multiple Myeloma.
Centers of Excellence in other cancers—lung cancer, breast cancer, prostate cancer, head and neck cancer, and adult blood cancers and myeloid disorders—will be introduced throughout the year. 

Related Press Releases:

Appointment to American Board of Obstetrics
and Gynecology
Stephanie Blank, MD , was appointed in July as a Subspecialty Division Member in the Division of Gynecologic Oncology of the American Board of Obstetrics and Gynecology (ABOG). Recognized by the American Board of Medical Specialties, the ABOG board certifies obstetricians and gynecologists. Dr. Blank also serves as Secretary-Treasurer of the Society of Gynecologic Oncology.
Perlman Family CCARE Lynch Syndrome Research Prize 
Theofano Orfanelli, MD, received the Perlman Family CCARE Lynch Syndrome Research Prize from the Foundation for Women’s Cancer (FWC) during the Society of Gynecologic Oncology’s 50 th Annual Meeting on Women’s Cancer. The FWC Research Grants and Awards program funds innovative research that shows promise for significant breakthroughs and fosters the careers of young investigators dedicated to gynecologic cancer research.

Last year, Nimesh Nagarsheth, MD , received the 2018 Public Service Award from FWC for his work with the band N.E.D. (No Evidence of Disease). 
American Society of Hematology Physician-Scientist
Career Development Award
Kaitlyn Ben-David, a third-year student in the five-year MD/MSCR (Master of Science in clinical research) Patient-Oriented Research Training and Leadership (PORTAL) program , is one of five medical students in the United States and Canada to receive the 2019-2020 American Society of Hematology (ASH) Physician-Scientist Career Development Award . The award allows students to gain a full year of experience in hematology research under the mentorship of an ASH member. A 2018 TCI Scholar, Kaitlyn is conducting research with James Ferrara, MD , on analyzing a phase II trial of natalizumab and steroids versus steroids alone as primary treatment for high-risk graft-versus-host disease (GVHD) defined by biomarkers. Natalizumab is a monoclonal antibody that blocks T cell migration into the gastrointestinal (GI) tract and is thus a potential drug for GI GVHD. Kaitlyn’s mentorship team includes Umut Ozbek, PhD , and John Levine, MD , as well as Dr. Ferrara. Kaitlyn plans to pursue pediatric hematology/oncology with a focus on innovative clinical trials for childhood cancers.
Congratulations to the 2019 “Next Gen Innovators”
They join a select group of early career hematologists and oncologists who are advancing their field through innovative approaches in the clinical and research settings.
Exploring the link between lung cancer lineage heterogeneity
and microenvironment
Hideo Watanabe, MD, PhD, Assistant Professor with the Division of Pulmonary, Critical Care and Sleep Medicine and the Department of Genetics and Genomic Sciences, has received a Lung Cancer Research Program Career Development Award from the Department of Defense for “Exploring the link between lung cancer lineage heterogeneity and microenvironment.” The proposed research aims to identify different lineage state subclasses of lung cancers that interact with their neighboring cells, increase understanding of the interaction mechanisms, and examine how dynamic changes within the tumor can occur during the course of cancer development and response to treatment. The interaction at the molecular level between lung cancer cells and surrounding cells in the microenvironment may provide a target for therapeutic intervention.
Preventing metastasis by targeting dormant disseminated tumor cells
Julio Aguirre-Ghiso, PhD, has received renewed funding from the Samuel Waxman Cancer Research Foundation for his research on preventing metastasis by targeting dormant disseminated tumor cells.

Recent findings made by Dr. Aguirre-Guiso and colleagues across two countries and six institutions:
  • Restoration of vitamin A signaling can activate tumor cell dormancy.
  • Dormancy programs are activated by host homoestatic signals that turn on senescence programs and specific epigenetic changes.
  •  Specific chromatic remodelers can induce dormancy of malignant cancer cells.
  • Cancer cells that disseminate early in cancer evolution can activate a novel dormancy mechanism distinct from that observed in more progressed cancers.
  • Awakening from dormancy is influenced by age-related immune factors.

Continued research will include a focus on the relationship of the immune microenvironment during early and late stages of cancer progression.
F30 Awards
at the Icahn School of Medicine at Mount Sinai have received F30 funding
from the NCI:

New Funding Opportunities
In support of the Patient Engagement and Cancer Genome Sequencing (PE-CGS) Network of the Cancer Moonshot SM
  • Several U2C Research Centers (RFA-CA-19-045) focused on addressing unique research knowledge gaps in the genomic characterizations of tumors
  • One U24 Coordinating Center (RFA-CA-19-046), which will facilitate trans-network collaborative activities
Application Due Date: October 30
Welcome to Our New Faculty
Natalie Berger, MD, joined Mount Sinai in July as Assistant Professor of Medicine, Hematology and Medical Oncology. Based at Mount Sinai West, Dr. Berger focuses on solid tumor oncology, particularly GYN and Breast Medical Oncology. Dr. Berger completed a fellowship in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai and a residency in Internal Medicine at the University of Connecticut Health Center. She earned her medical degree from St. George’s University School of Medicine in Grenada. Dr. Berger is conducting research aimed at identifying patients with triple negative breast cancer who have residual disease and are most likely to benefit from adjuvant checkpoint inhibitor therapy. She is also conducting research on quality improvement.
Deborah Doroshow, MD, PhD, joined Mount Sinai in August as Assistant Professor of Medicine, Hematology and Medical Oncology. Based at The Mount Sinai Hospital, Dr. Doroshow sees patients with lung cancer and a variety of solid tumors, as well as patients enrolled on phase 1 clinical trials through the Center for Novel Therapeutics. She completed a fellowship in Hematology and Oncology and a residency in Internal Medicine at Yale University School of Medicine. Dr. Doroshow received her medical degree from Harvard Medical School and earned a PhD in History from the Program in the History of Science and Medicine at Yale. 
New TCI Seminar Series Co-director
For the past six years, Jerry Chipuk, PhD, and Emily Bernstein, PhD, have successfully co-directed the Tisch Cancer Institute Seminar Series (every Tuesday at noon), working closely with faculty, post-doctoral fellows, students, and administration to expand the series and integrate a broad array of presenters. Dr. Bernstein stepped down from her co-director role in July. Amaia Lujambio, PhD, has assumed the position and is working with Dr. Chipuk to continue the excellence of the program, focused on basic and translational cancer biology. 

Research Faculty Representative
Doris Germain, PhD , has taken on the role of Hem/Onc Research Faculty Representative for Infrastructure and Communications As such, Dr. Germain will work to enhance communication among faculty, trainees, students, laboratory staff and administration, and facilitate compliance with safety regulations.
Dr. Germain is the co-director of the Cancer Biology Training Program and a member of the Cancer Mechanisms Program. Her research on breast cancer focuses on development of improved endocrine therapies, the role of the mitochondrial heterogeneity in breast cancer progression, and the link between pregnancy and breast cancer.
Oral selinexor-dexamethasone for triple-class refractory
multiple myeloma

Ajai Chari, MD, and Sundar Jagannath, MBBS,
are lead authors of a report in the New England Journal of Medicine (NEJM) on a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that demonstrated a significant overall response rate in multiple myeloma patients with triple-class refractory disease. These patients do not respond to currently available proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies, and they typically experience short overall survival.
The SINE compound selinexor binds to the nuclear export protein Exportin 1 (XPO1), which is overexpressed in myeloma and correlates with poor prognosis, and blocks its function, leading to apoptosis in the malignant cells. 

Anti-tumor T-cell homeostatic activation is uncoupled from homeostatic inhibition by checkpoint blockade
Joshua Brody, MD , et al.

Researchers investigated the unconventional use of dual checkpoint blockade (dCB) during adoptive T cell transfer post-lymphodepletion. Findings indicate that dCB protects transplanted T-cells from inhibitory signaling and potentiates their homeostatic activation. This increased T-cell activation from the combination of transfer and dCB—referred to as “immunotransplant”—significantly amplified anti-tumor immune responses resulting in durable tumor regressions in lymphoma, lung cancer, and melanoma, even when dCB alone yielded no apparent anti-tumor effect. These findings reveal a novel T-cell regulatory mechanism and suggest a therapeutic approach for checkpoint-refractory tumors, now in clinical trial for patients with aggressive non-Hodgkin lymphomas ( NCT03305445).
SOD1 is essential for oncogene-driven mammary tumor formation but dispensable for normal development and proliferation

This study investigated the role of the dismutase SOD1 in mammary gland tumorigenesis as well as in normal mammary gland development. Results identify SOD1 as an ideal target for cancer therapy since SOD1 inhibitors hold the potential to prevent the growth of cancer cells of diverse genotypes while sparing normal tissues. SOD1 may be a universal target by affecting a housekeeping function rather than a specific oncogenic driver.
Oncogenic G12D mutation alters local conformations and dynamics
of K-Ras

This detailed description of G12D mutation effects on the local dynamic characteristics of both active and inactive protein helps enhance our understanding of local K-Ras dynamics, and can inform studies on the development of direct inhibitors towards the treatment of K-Ras G12D -driven cancers.
Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial

This study provides valuable data and support for performing Phase 3 trials utilizing induction chemotherapy to reduce chemoradiotherapy dose, and thereby reduce toxicity, in patients with locally advanced Human Papillomavirus oropharyngeal carcinoma.
Oral idasanutlin in patients with polycythemia vera
et al.

This article reports on an investigator-initiated phase 1 trial of the oral MDM2 antagonist, idasanutlin , in patients with high-risk polycythemia vera (PV) and essential thrombocytopenia who had failed at least one prior therapy. Results demonstrating a high degree of clinical efficacy indicate that idasanutlin is a promising novel agent for PV and have led to a global phase 2 trial .
Fibroblast growth factor receptor 3 alterations and response to PD-1/PD-L1 blockade in patients with metastatic urothelial cancer

Findings demonstrate that FGFR3 mutation status in urothelial cancers (UC) is not a biomarker of resistance to checkpoint inhibition (CPI). Single-agent activity of both FGFR3 inhibitors and CPI in FGFR3-mutant UC and potential non-cross resistance provide a rationale for combination approaches.
The natural history of untreated muscle invasive bladder cancer

This study describes the natural history of untreated muscle invasive bladder cancer (MIBC) and compares the oncological outcomes of treated and untreated patients. Findings, which indicate that untreated patients with MIBC are at very high risk for near term cancer specific mortality, may inform integrating curative intent therapy, particularly in older patients.
Genetic disarray follows mutant KLF1-E325K expression in a congenital dyserythropoieticanemia patient

Researchers expanded erythroid cells from a CDA type IV patient’s peripheral blood and analyzed its global RNA expression pattern. They found that a large number of erythroid pathways were disrupted, particularly those related to membrane transport, globin regulation, and iron utilization. The altered genetics led to significant deficits in differentiation.
Blastic plasmacytoid dendritic cell neoplasm-current insights

In this report, the authors review etiology, summarize diagnostic criteria, and discuss historic treatments and novel therapies for blastic plasmacytoid dendritic cell neoplasm. They note that advances in pathobiological understanding and progress in immunotherapeutic options offer promise for novel therapeutic strategies for patients with this rare malignancy that has universally poor outcomes. 
The Lloyd Sherman Scholars Program
This past summer (second summer in a row), The Tisch Cancer Institute supported two student interns for The Lloyd Sherman Scholars Program through the Center for Excellence in Youth Education (CEYE), a unit of Mount Sinai’s Office for Diversity and Inclusion. The Scholars Program, which provides stipends for both students and mentors, is for high school-aged boys belonging to groups that are under-represented in medicine.

William Winston worked in the laboratory of Ross Cagan, PhD ,   Director of the Center for Personalized Cancer Therapeutics, to establish Drosophila models of RASopathies, a rare inherited disease that leads to developmental defects including skeletal defects, cognitive deficits, and heart defects. William established specific RASopathy lines and optimized them as a platform for whole animal drug screening, resulting in multiple candidate screening lines.
Jeremy Baidoo worked in the laboratory of Marek Mlodzik, PhD , Chair of Cell, Developmental and Regenerative Biology. He investigated, under the supervision of Giovanna Collu, PhD , how the CG3711 gene affects RAS production by identifying phenotypes in Drosophila, with an ultimate goal of limiting RAS mutations in cancers.

William and Jeremy are both seniors at the Manhattan Center for Science and Mathematics.
The Division of Hematology and Medical Oncology welcomed
TCI Diversity and Inclusion News
The Diversity and Inclusion Subcommittee of the TCI Education and Career Development Committee (part of TCI’s Cancer Research Career Enhancement and Related Activities Core ) provides recommendations to foster recruitment and retention of talented, underrepresented minority cancer researchers and promote evidence-based knowledge about cancer disparities among TCI investigators. 

Ann-Gel Palermo, Dr PH—a member of Mount Sinai’s Office for Diversity and Inclusion (ODI) Executive Leadership Team—recently joined the TCI Diversity Subcommittee. She will be instrumental in enhancing alignment of the TCI Diversity Subcommittee with ODI.

Other members of the TCI Diversity Subcommittee are: Brian Brown, PhD ; Jerry Chipuk, PhD ; Janice Gabrilove, MD ; Sandra Hatem; Cathie Pfleger, PhD; and Cardinale Smith, MD, PhD.
The TCI Diversity and Inclusion subcommittee is seeking new members. If you are interested, please respond here or contact Rhaisili Rosario .

The Future of Advanced Prostate Cancer
William Oh, MD, presented at the Advanced Prostate Cancer Consensus Conference: APCCC 2019 , held August 29-31 in Basel, Switzerland. Dr. Oh spoke on the future of advanced prostate cancer management in polymetastatic prostate cancer, and discussed follow-up on androgen deprivation therapy (ADT) alone versus ADT “plus” novel therapies. In addition, Dr. Oh served on an interdisciplinary expert panel that voted at the end of the conference on pre-defined consensus questions targeting areas of clinical relevance. Dr. Oh has served on the panel at all three biennial conferences, with the first initiated in 2015 to provide a forum to discuss current questions on the clinical management of men with advanced prostate cancer.
Global Cancer Care
Michail Shafir, MD, MPH, Clinical Professor of Surgery and Oncological Sciences, served as faculty at ASCO’s Multidisciplinary Cancer Management Course (MCMC) in Paraguay, organized in collaboration with City Cancer Challenge. Dr. Shafir spoke on breast cancer surgery and moderated discussions about breast cancer cases presented by local oncologists. The goal of MCMCs is to improve cancer care globally.
Therapeutic options for patients

Joshua Richter, MD, presented on therapeutic options for patients with multiple myeloma in conjuction with the Internatonal Myeloma Workshop 2019 in Boston. Dr. Richter is Assistant Professor of Medicine, Hematology and Medical Oncology, with the Center of Excellence for Multiple Myeloma. He serves as director of myeloma services at The Blavatnik Family – Chelsea Medical Center at Mount Sinai.
TCI Summer Outreach Team
With the help of summer interns—some through the Northeast Regional Alliance (NERA) MedPrep HCOP Academy Program and some through CUNY—TCI successfully recruited 1,200 residents of East Harlem, Central Harlem, and the Upper East Side to participate in The Community Cancer Needs Survey. Information about health and cancer prevention behaviors obtained through the survey will inform strategies to better meet the needs of our catchment area population and reduce disparities in cancer care. 
What You Need to Know About Being Diagnosed with Cancer
A complimentary educational session for our local communities

Thursday, September 26, 5 to 7:30 pm
Hess, Second Floor

The Myeloproliferative Neoplasms Research Consortium 
The Myeloproliferative Neoplasms Research Consortium (MPN-RC)—an international, multi-institutional consortium funded by the National Cancer Institute—has a new website that highlights the consortium’s collaborative efforts to develop and evaluate treatments that will improve the survival of patients with myeloproliferative neoplasms.

Ronald Hoffman, MD, leads Project 3: Development of Strategies to Deplete Myelofibrosis Cells, and the Administrative Core. John Mascarenhas, MD, is principal investigator on Project 4: MPN-RC Clinical Consortium.

Clinical trials feature a first in human, open-label, multicenter, Phase I/Ib trial of AVID200 , a TGF-Beta inhibitor, and a research tissue bank .
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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.  , 929-237-5802
    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.