January 2022
New Center of Excellence
The Center of Excellence for Blood Cancers and Myeloid Disorders is the newest cancer center of excellence at TCI. Under the leadership of John Mascarenhas, MD, the center uses genetic, epigenetic, cell signaling, and immunologic factors in developing individualized treatment plans. At the forefront of blood cancer research, the center's physicians and researchers pioneer new forms of cellular therapy such as vaccines, bispecific antibodies, CAR T-cell therapies (led by Keren Osman, MD), and natural killer cell-based therapies.

Featured Publication and Research
Cancer. 2021 Dec 1. PMID: 34379804

Treatment de-escalation for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is critically important, as the current standard-of-care treatment, developed for HPV-negative cancers, is highly morbid and negatively impacts long-term quality of life. The justification for treatment de-escalation is based on outstanding treatment outcomes in HPV-positive OPSCC. However, lack of meaningful inclusion criteria and stratification for patients and coordination of the selection of therapies for phase 3 trials has significantly impeded progress. In this commentary, the authors propose a strategy that features several adequately powered, stratified, coordinated, multicenter, and multidisciplinary randomized controlled trials that compare rationally selected de-escalation strategies in well-defined risk groups.
Mount Sinai’s head and neck oncology program is actively and aggressively pursuing de-escalation studies in HPV positive oropharynx cancer. Current clinical trials include surgical therapy for patients with early-stage disease followed by risk-based deescalated radiation therapy, and a risk-based de-escalation radiation therapy study for patients who are ineligible for surgery due to functional or structural contraindications. The program is also conducting a sequential trial of induction chemotherapy followed by de-escalated chemo radiotherapy for patients with locally advanced disease with poor prognostic features. These trials have already proven successful and provide the opportunity to treat patients with less radiation therapy with confidence regarding the outcomes.
New Faculty
Juan Martín Arriaga, PhD, has joined Mount Sinai as Assistant Professor of Oncological Sciences. His laboratory will focus on identifying the epigenetic alterations that drive prostate cancer to metastasize to bone and developing novel therapeutics. During his post-doctoral training, Dr. Arriaga developed a unique genetically engineered mouse model of prostate cancer that spontaneously metastasizes to bone; this led to the identification of a powerful gene signature (termed META-16 and patented) that can identify localized prostate cancer tumors at high risk of developing metastasis.
Most recently, Dr. Arriaga was an Associate Research Scientist in the Department of Molecular Pharmacology and Therapeutics at the Herbert Irving Comprehensive Cancer Center at Columbia, where he also did his post-doctoral training. He earned his PhD at the School of Biochemistry and Pharmacy at the University of Buenos Aires. Dr. Arriaga was honored with a 2021-2023 Young Investigator Award from the Prostate Cancer Foundation. 
Faculty News
Cardinale Smith, MD, PhD, has been elected as a new member of the Nominating Committee of the American Association of Clinical Oncology (ASCO) for a three-year term, beginning June 2022. Members of the Nominating Committee are tasked with developing a slate of candidates for elected ASCO positions.

Congratulations to the following on their recent promotions at the Icahn School of Medicine at Mount Sinai:

Stephanie Blank, MD, is taking on the role of Associate Director of Women’s Cancers for The Tisch Cancer Institute. As such, she will be instrumental in encouraging translational research for women’s cancers, including development of clinical trials that address treatment challenges and improved outcomes and that are accessible to our diverse patient population.
Hanna Irie, MD, PhD, is collaborating with EpiAxis Therapeutics on a pre-clinical investigation focused on inhibiting Protein Kinase C theta (PKC theta) in breast cancer models. PKC theta, which is upregulated in a variety of cancers, is associated with tumor aggressiveness, metastasis, and resistance to therapy. The aim is to validate novel inhibitors against PKC theta for triple negative breast cancer, with the goal of translating the inhibitors into clinical application.
Grant Awards
Arvin Dar, PhDErnesto Guccione, PhD, and Amaia Lujambio, PhD, were awarded grant funding from the National Cancer Institute to identify new biological targets for precision-based therapeutics for hepatocellular carcinoma. They aim to launch a clinical trial of WNTinib to better understand how it works and to develop secondary compounds that target other specific subtypes of liver cancer. In preliminary studies, they identified WNTinib, a novel small molecule inhibitor that can reduce the growth of tumors, as a strong lead.
Arvin Dar, PhD, and Ernesto Guccione, PhD, received an ASPIRE award from the Mark Foundation for Cancer Research for Target and Anti-Target Identification of Novel Lead Compounds from a Chemical Genetic Organoid Platform.” Dr. Dar and Dr. Guccione plan to identify the direct targets of new small molecule leads using genetic and chemoproteomic approaches and then leverage those insights to create improved compounds. ASPIRE (Accelerating Scientific Platforms and Innovative Research) awards support high-risk, high-reward projects that aim to answer key feasibility and proof-of-concept questions in an accelerated timeframe.
Aarti Bhardwaj, MD, Sofya Pintova, MD, Cardinale Smith, MD, PhD, Alana Noble-Kirk, MBA, and Mark Liu, MHA, have been awarded funding from the Office of Well-Being and Resilience at the Icahn School of Medicine at Mount Sinai for “Better Together – A team-based approach to improve prior authorization efficiencies and promoting physician wellness.” The project is focused on utilizing an FTE resource under the cancer registry team to enter into EPIC data that is already being captured by the registry. The goals are to enhance the patient experience and relieve faculty distress by expediting prior authorizations, and enhance access to staging data that can assist with research.
Nina Bickell, MD, Stephanie Blank, MD, and Chung Yin Kong, PhD, were awarded Cancer Intervention and Surveillance Modelling Network (CISNET) U01 funding from the National Cancer Institute in collaboration with Columbia and Duke Universities. Their project, Comparative Modeling for the Prevention and Control of Uterine Cancer, aims to create population-level advanced simulation models of uterine cancer as decision tools for health policymakers in determining optimal cancer prevention and control interventions. 
Nina Bhardwaj, MD, PhD, has been awarded funding as part of extramural member researcher participation in the Parker Institute for Cancer Immunotherapy consortium. Dr. Bhardwaj’s research aims to fully characterize the immunogenic properties of neoantigens derived from shared frameshift mutations (identified by Dr. Bhardwaj’s laboratory) in order to guide the design of off-the-shelf cancer vaccines that can be utilized in therapeutic and preventative settings in MSI-H cancers and Lynch Syndrome.
Jian Jin, PhD, and Greg Wang, PhD, at the University of North Carolina, have been awarded R01 funding from the National Cancer Institute to dissect and target canonical and non-canonical oncogenic functions of EZH2, a histone methyltransferase, in cancer. They recently found that EZH2 has a non-canonical function in activation of oncogenes in mixed-lineage leukemia (MLL)-rearranged leukemias, which differs from the canonical function of EZH2 related to gene repression. Dr. Jin, Dr. Wang, and team aim to develop and optimize novel EZH2 PROTAC degraders that effectively suppress both canonical and non-canonical oncogenic activities of EZH2 as a therapeutic strategy for treating MLL-rearranged leukemias.

Grant Opportunities
Request for Ovarian Cancer Research Proposals
Department of Obstetrics, Gynecology and Reproductive Science and The Tisch Cancer Institute
Basic science, translational, epidemiological, behavioral, health disparity and other research topics will be considered.
Application Due Date: January 28, 2022

The American Cancer Society will conduct a virtual Extramural Discovery Science Grants Workshop with a focus on grant opportunities and grantsmanship tips. Wednesday, February 9, 2 pm.


JAMA Network Open. 2021 Dec 1. PMID: 34919136
This cohort study of 312,382 patients found that population-level mortality for non-small cell lung cancer has decreased from 2006 to 2016. Although advances in treatments, particularly targeted therapeutics, have played a role in affecting mortality, this analysis suggests that decreased mortality is also associated with a diagnostic shift from later to earlier stage disease and a histology shift to adenocarcinoma. Findings reinforce the importance of screening in the early detection, intervention, and effective treatment of cancer.
Nature Medicine. 2021 December. PMID: 34893771

B-cell maturation antigen (BCMA) is a prominent tumor-associated target for CAR T-cell therapy in multiple myeloma (MM). This paper reports on a patient with MM who developed a progressive movement disorder with features of parkinsonism following ciltacabtagene autoleucel BCMA-targeted CAR T-cell infusion. The authors identified differences in the CAR T in the patient leading to increased persistence by single cell sequencing as well as BCMA expression in both the brain from the patient and additional healthy brains. The case shows the potential of BCMA-targeted CAR T cells to cross the blood-brain barrier in a subset of patients and cause a progressive neurocognitive and movement disorder, possibly through targeting of BCMA-expressing cells of the basal ganglia. Findings suggest that anti-BCMA CAR T-cell therapies, although effective in MM, warrant close monitoring for neurotoxicity.

Nature Cancer. 2021 Dec 13.

This study revealed that disseminated tumor cells secrete collagen type III and generate a collagen extracellular matrix that favors dormancy, and that the transition from dormancy to reactivation is accompanied by changes in the collagen three-dimensional architecture. The researchers found that the collagen receptor DDR1 is upregulated upon dormancy onset and that DDR1 expression is required to maintain tumor dormancy through its binding to collagen III. The findings may lead to a biomarker to predict tumor recurrences and therapeutic intervention to reduce local relapses.

Cells. 2021 Dec 6. PMID: 34943938
This study investigated the role of TMEM176B—a member of the membrane spanning 4-domains (MS4) family of transmembrane proteins—in breast cancer. Results suggest that TMEM176B expression in breast cancer cells regulates key signaling pathways and genes that contribute to cancer cell growth and progression, and is a potential target for therapeutic antibodies. Targeting TMEM176B may enhance the anti-tumor immune response to immune checkpoint inhibitors and also directly inhibit tumor cell growth.
Sacha Gnjatic, PhD, presented at the Department of Pathology Grand Rounds at Memorial Sloan Kettering Cancer Center on November 19: “Defining Immune Correlates of Cancer Immunotherapy in Tissues and Blood Using Single-Cell High-Dimensional Approaches.” In addition, Dr. Gnjatic was the featured guest at the Pathology Fellows’ Session.
Hematology and Medical Oncology Grand Rounds
January 27, 2022, 8:30 am
Presenter: Ashish Kamat, MD, Professor of Urologic Oncology (Surgery) and Cancer Research, MD Anderson Cancer Center
Topic: Current Treatment Landscape of Non-Muscle-Invasive Bladder Cancer
ASCO Abstract Submission Deadline:
February 15, 2022
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