Ovarian cancer is the most lethal of all of the gynecologic cancers. The vast majority of patients present with stage III/IV disease, and while 75 percent with advanced disease achieve a clinical complete response, recurrence is common, usually within 18 months. Therefore, a key goal in the treatment of ovarian cancer is to advance effective maintenance therapy regimens as well as strategies to prevent recurrence.
The mainstay of treatment for advanced ovarian cancer is surgery and chemotherapy. Upon recurrence, patients have been stratified based on response (or non-response) to platinum-based chemotherapeutic agents. New approaches include the use of biologics—anti-angiogenic agents and PARP inhibitors. Patients can now be characterized based on genetic predisposition, such as BRCA 1 and 2 mutations, and molecular profiling; such patients now receive front line maintenance with a PARP inhibitor, a maintenance regimen that has shown unprecedented progression free survival advantage. Additionally, anti-angiogenic agents are now used for maintenance in patients not receiving PARP inhibitors. At recurrence, the molecular characteristics of a patient’s tumor can inform a treatment best suited for her; these therapies include the PARP inhibitors and anti-angiogenics as well as immunotherapy and antibody-derived conjugates.
Current studies focus on combinations of immune checkpoint inhibitors and other biologics, such as PARP inhibitors, vascular endothelial growth factor (VEGF) inhibitors, and antibody derived conjugates (for example, NCT02839707, NCT03657043, and NCT03602859 ).
While PARP inhibitors have been FDA approved for 4.5 years, they were only recently approved for maintenance therapy in late 2018. 

“This is an exciting time in novel therapeutics for ovarian cancer, with approval of new agents, a focus on maintenance therapy, and improved options for treatment that support a better quality of life,” says Stephanie V. Blank, MD , Director of Gynecologic Oncology for the Mount Sinai Health System, Director of Oncology Programs for the Blavatnik Family Women’s Health Research Institute, and Director of the Women's Cancer Program at The Blavatnik Family – Chelsea Medical Center at Mount Sinai.

Another target for novel therapy is the PI3K/AKT signaling pathway. Amy Tiersten, MD , Clinical Director of Breast Medical Oncology at the Dubin Breast Center, is the Principal Investigator for a pending clinical trial using ipatasertib, an AKT inhibitor: “Open label phase II study to evaluate the safety and efficacy of ipatasertib in combination with paclitaxel in platinum-resistant recurrent epithelial ovarian cancer.”
In collaboration with Tom Marron, MD, PhD , and Novel Therapeutics , Dr. Blank and Dr. Tiersten and colleagues are developing a robust portfolio of clinical trials that offer more options than ever before for women with ovarian cancer. 

Additional areas of research include a focus on patients who had been exposed to PARP inhibitors but developed resistance ( NCT03704467 ), and combining immune modulators with other agents to make ovarian cancer, which is generally not especially immunogenic, more susceptible to an immune-based approach ( NCT03602859 ). 
American Research Training Award for Fellows
Bridget Marcellino, MD, PhD, has been awarded a Research Training Award for Fellows (RTAF) from the American Society of Hematology. The award provides $70,000 for protected research time for a one-year period.

Dr. Marcellino is a graduate of the MD/PhD Program at the Icahn School of Medicine at Mount Sinai and completed her fellowship in Hematology/Medical Oncology at Mount Sinai this year; she was Chief Fellow in 2017-2018. 
Excellence in Teaching Award
Congratulations to Arielle Langer, MD, MPH, 2018-2019 Chief Fellow, Hematology/Medical Oncology , for receiving a 2019 House Staff Excellence in Teaching Award from the Icahn School of Medicine at Mount Sinai. The annual Excellence in Teaching Awards honor outstanding educators across the Mount Sinai Health System, including faculty, trainees, students, and staff.
Selected for Membership in Alpha Omega Alpha
Congratulations to Brett Miles, DDS, MD , Professor of Otolaryngology, and Anish Parikh, MD, 2018-2019 Chief Fellow, Hematology/Medical Oncology , who were selected for membership in Alpha Omega Alpha . A lifelong honor, membership in Alpha Omega Alpha confers recognition for a physician's dedication to the profession and art of healing. An induction ceremony and reception will take place on Tuesday, June 11, at 4:30 pm in the Davis Auditorium.
Alumnus Humanitarian Award
Louis M. Aledort, MD, has been selected by the University of Rochester Medical Center, where he trained as a resident, to receive the 2019 Alumnus Humanitarian Award for his lifetime commitment to finding a cure for hemophilia and other clotting disorders. Dr. Aledort joined Mount Sinai in 1966. He served as Dean for Faculty and Hospital Affairs at Mount Sinai School of Medicine (now the Icahn School of Medicine at Mount Sinai), and has been the Mary Weinfeld Professor of Clinical Research in Hemophilia since 1993. In 2011, Dr. Aledort was recognized by the Einstein Alumni Association with its Lifetime Achievement Award; he was a member the first graduating class of Albert Einstein College of Medicine. He received the Lifetime Achievement Award from the Hemostasis and Thrombosis Research Society in 2010. Aledort also holds an honorary doctorate in medicine from Lund University in Sweden.

Artificial Intelligence in Biology and Medicine
Green denotes abnormal ring fragments indicative of cancer
Two articles on artificial intelligence (AI) in biology and medicine appeared recently in the Wall Street Journal and The Scientist . They feature work from the Center for Computational and Systems Pathology , led by Carlos Cordon-Cardo, MD, PhD , System Chair, Department of Pathology, and colleagues at the Icahn School of Medicine at Mount Sinai, on AI enabling pathology tools and algorithms, including an innovative prostate cancer AI-automated Gleason grading and quantitation of abnormal proteins in Alzheimer’s disease.
MDM2 Integrates Cellular Respiration and Apoptotic Signaling Through NDUFS1 and the Mitochondrial Network 

Results of this study show that MDM2, a gene commonly amplified in cancer, alters cellular metabolism influencing energy production, stress signaling, and cell survival pathways. This newly discovered biological mechanism will impact future patient care by providing a clearer understanding of the role of MDM2 amplification in disease. Additionally, MDM2’s regulation of mitochondrial biology engages an understanding of cell metabolism which promises to be useful in cancer diagnosis and treatment, and influence drug discovery and development of new therapeutic options.  
The Evolving and Multidisciplinary Considerations in Nodal Radiation in Breast Cancer

This paper describes the role of regional nodal irradiation in the context of the de-escalation of axillary surgery, improved understanding of the molecular and pathologic features of breast cancer, and increasing use of neoadjuvant chemotherapy. It also summarizes key clinical trials aimed at optimizing the management of regional lymph nodes in concert with the ultimate goal of assessing each patient’s risk for recurrence and individualizing multidisciplinary management for improved clinical outcomes.
Parity Predisposes Breasts to the Oncogenic Action of PAPP-A
and Activation of the Collagen Receptor DDR2

Study data indicate that history of pregnancy and lactation, combined with the expression of pregnancy-associated plasma protein A (PAPP-A)-driven genetic signature, holds the potential to identify patients at higher risk of metastatic disease and develop targeted intervention.
Functional Screening to Identify Senescence Regulators in Cancer

Cellular senescence —irreversible cell cycle arrest —can occur in response to several triggers, in different cell types and tissues, including cancer cells, and entails a number of phenotypes and effector mechanisms.  This review focuses on work performed over the last few years, emerging technologies, and future perspectives in the field of functional screening to study senescence in cancer and harness it to our advantage.
Relevant Updates in Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare myeloproliferative neoplasm characterized by a clonal proliferation of mast cells and their subsequent infiltration of either the bone marrow or extracutaneous, extramedullary sites. Increased recognition of SM and increased understanding of its biology have led to the translation of mechanism-based targeted therapies. For example, the recent approval of the KIT inhibitor, midostuarin, has spurred development of other kinase inhibitors targeting signaling pathways. This article describes the pathogenesis, epidemiology, and diagnosis of SM, and provides an update on current treatment and future therapies in development.
Outcomes of Older Patients with Pulmonary Fibrosis and Non-Small
Cell Lung Cancer

This study, based on review of 54,453 non-small cell lung cancer patients (NSCLC), found that patients with idiopathic pulmonary fibrosis (IPF) and NSCLC have a greater proportion of early stage disease of squamous histology in a lower lobe distribution—a factor that may need to be incorporated into risk models for lung nodule management in IPF patients—and that IPF is an independent factor for increased NSCLC and overall mortality. The study reinforces the need for further research to identify the best strategies to control and treat NSCLC in patients with IPF.
Associate Chief of Breast Services at Mount Sinai West
Jennifer Casher Lehman, MD, FACS, has joined Mount Sinai as Associate Chief of Breast Services at Mount Sinai West and Mount Sinai St. Luke’s, and as Assistant Professor of Surgery at the Icahn School of Medicine at Mount Sinai. She specializes in benign and malignant breast disease, preventative surgery for women at high risk, and oncoplastic approaches to breast surgery. Dr. Lehman received her medical degree from the Stony Brook University School of Medicine. She completed residency training in general surgery at NewYork-Presbyterian Hospital / Columbia University Medical Center—including a research year fellowship in surgical critical care at Jackson Memorial Hospital, Ryder Trauma Center in Miami—and a fellowship in breast surgical oncology at Memorial Sloan Kettering Cancer Center. Prior to joining Mount Sinai, Dr. Lehman had been with the Institute of Comprehensive Breast Care at Lenox Hill Hospital / Northwell Cancer Institute since 2012. 
Vice President of Oncology Nursing Services
Wendy R. Miano, DNP, RN, AOCN, NEA-BC, has joined the Mount Sinai Health System as Vice President of Oncology Nursing Services. Dr. Miano began her oncology nursing career in 1984 on an adult bone marrow transplant unit at the University Hospitals Cleveland Medical Center and served for the past 11 years as Chief Nursing Officer/Director of Nursing at University Hospitals Seidman Cancer Center, affiliated with Case Comprehensive Cancer Center in Cleveland. Dr. Miano received her MSN (pediatric oncology focus) and DNP at Case Western Reserve University Frances Payne Bolton School of Nursing. “As an experienced oncology nursing leader, I am honored be part of Mount Sinai’s Oncology Service Line leadership team that exhibits a passion for research and clinical excellence and that embraces patients and families as true partners in care.”
Extending Patient Care
Starting in early April, the Oncology Care Unit (OCU), located on the second floor of the Guggenheim Pavilion at The Mount Sinai Hospital, extended its operations to 24 hours a day, 7 days a week. Staffed by oncology nurse practitioners and nurses, the OCU provides access to specialized outpatient services for cancer patients with urgent medical needs, thereby decreasing Emergency Department and hospital admissions. 
Mobile Mammography is on the go almost every day. Patients are encouraged to make appointments in advance, although walk-ins can usually be seen.
Curing Metastatic Colorectal Cancer:  Turning Hope Into Reality
Organized by Sofya Pintova, MD
Thursday, May 16, 2019
6–9 pm

Reservations are still being accepted—contact Sonia Heras
The Changing Landscape of Diagnostic Biomarkers: Exploring the One-Biomarker-per-Drug Paradigm in Oncology
Sacha Gnjatic, PhD , David Rimm, MD, PhD (Yale) and Houssein Abdul Sater, MD (NCI)

Scott L. Friedman, MD , Co-director of the Liver Cancer Program and Dean for Therapeutic Discovery, was an invited speaker at the Liver Fibrosis to Cancer Workshop at the National Cancer Institute, April 22-23. Dr. Friedman presented “Linking Fibrosis to Hepatocellular Carcinoma—The Role of Hepatic Stellate Cells.”

November 12, 2019 at 9 am-6 pm
Keynote Speaker:
University Medical Center Utrecht
Abstract submissions are invited for a poster session. Submission deadline: 
September 17, 2019
June 14 , 2019 at 1-6 pm
Columbia University
This conference will provide a forum for researchers and students from NYC's cancer centers to discuss cancer prevention and control in NYC and facilitate collaborative projects aimed at alleviating cancer disparities.
Due date for abstracts for the poster session: May 30, 2019

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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.