March 2023

Praveen Raju, MD, PhD, and colleagues

P-selectin-targeted nanocarriers induce active crossing of the blood–brain barrier via caveolin-1-dependent transcytosis

Nature Materials. 2023 Mar 2. PMID: 36864161

Dr. Raju and colleagues report on a newly-developed blood-brain barrier penetrating drug delivery approach that uses nanoparticles for targeted delivery of anti-cancer drugs to treat pediatric brain tumors. Using a homing mechanism found within brain tumor blood vessels and used by immune cells to know where they are needed, the researchers were able to effectively deliver lower drug doses of a promising therapeutic agent to specific tumor sites while sparing the on-target bone toxicity experienced by pediatric patients. They also showed that the targeted drug delivery is further enhanced by low dose radiation, which is standard of care for most children and adults with both primary and metastatic brain tumors. Overall, findings demonstrate a potent strategy for targeted intracranial pharmacodelivery that overcomes the restrictive blood-brain barrier to achieve enhanced tumor-selective penetration.

Press Release

Miriam Merad, MD, PhD, has started a three-year term as president of the International Union of Immunological Societies (IUIS). IUIS is an umbrella organization for many of the regional and national societies of immunology throughout the world. There are currently 88 member societies representing more than 60,000 immunologists.

Read Dr. Merad's Address

Ramon Parsons, MD, PhD, will receive the 2023 Jacobi Medallion at a ceremony on March 15 at The Plaza Hotel. The Jacobi Medallion has been awarded since 1952 for distinguished contributions to the field of medicine or extraordinary service to The Mount Sinai Hospital, the Mount Sinai Health System, the Icahn School of Medicine at Mount Sinai, or the alumni community.

Jian Jin, PhD, received a GlaxoSmithKline (GSK) Inventor Award for Daprodustat, an oral medication that has been approved in the United States and Japan for the treatment of anemia caused by chronic kidney disease. Dr. Jin is one of several inventors of Daprodustat, a small-molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase.

GSK Press Release

Fred R. Hirsch, MD, PhD, will be presented with the Heine Hansen Lifetime Achievement Award 2022 by the European Society of Medical Oncology in recognition of his lifelong outstanding contribution to lung cancer research. The award ceremony will take place on March 29 at the European Lung Cancer meeting in Copenhagen. The ceremony was originally scheduled for last year in Prague, but was cancelled due to Ukraine.

Adriana Malone, MD, Director of Mount Sinai’s Hematology and Medical Oncology Fellowship Program, was honored with the 2023 Parker J. Palmer Courage to Teach Award from the Accreditation Council for Graduate Medical Education (ACGME). Dr. Malone and other award recipients were recognized at the 2023 ACGME Annual Education Conference, held February 23-25.



ACGME Interview with Dr. Malone

Congratulations to Angela Liu, MD, and Daniel Nathan, MD, incoming Chief Fellows for 2023-2024. They will take over for outgoing Chief Fellows, Rima Patel, MD, and Hannah Levavi, MD.

Fellowship Program Video

Alan Shih, MD, PhD, received a Basic/Translational Junior Faculty Award, part of the 2023 Scholar Awards from the American Society of Hematology (ASH). ASH Scholar Awards support early career investigators dedicated to hematology research as they transition from training programs to careers as independent investigators. Dr. Shih’s research is focused on understanding the mechanisms of leukemogenesis, particularly in epigenetics, and using mouse models to develop new treatment options. 

Elvin Wagenblast, PhD, is a recipient of the 2023 Damon Runyon-Rachleff Innovation Award. His project—"Untangling the Evolutionary Dependency of Childhood Leukemia"—will use human primary blood stem cells and CRISPR/Cas9-mediated genome engineering to model leukemia evolution and identify biological processes that specifically contribute towards cancer development in children. The Damon Runyon-Rachleff Innovation Award supports “high-risk, high-reward” ideas with the potential to significantly impact the prevention, diagnosis, or treatment of cancer. 

Scott Friedman, MD, and Saurabh Mehandru, MD, are Co-Principal Investigators on a new T32 Training Grant for postdoctoral fellows from the National Institute of Diabetes and Digestive and Kidney Diseases. “Training Program in Investigative Gastroenterology and Hepatology” will fund three trainees per year for five years, beginning April 1, 2023, and will focus on three broad areas:

• Gastrointestinal inflammation and the microbiome
• Non-alcoholic steatohepatitis (NASH), hepatic inflammation and fibrosis
• Genetics of gastrointestinal and liver diseases

Potential trainees or mentors should contact Dr. Friedman or Dr. Mehandru. Trainees must hold a MD, PhD, or MD/PhD, and be a U.S. Citizen or Permanent Resident.

Doris Germain, PhD, received a new R01 from the National Institute on Aging for “Understanding the Influence of Mitochondrial DNA Haplotypes on Breast Aging and Cancer.” This award builds on the longstanding interest of the Germain Lab in how breast cancer cells manage to maintain the integrity of their mitochondrial network, which is critical for their survival, despite intense oxidative and proteotoxic stress. Further, since alteration in mitochondrial functions is a hallmark of aging, this R01 will address these questions in mouse models that recapitulate aging in pre-, peri-, and post-menopausal women, as well as elderly women.

Santiago Thibaud, MD, received two research grant awards in support of "Screening for Pathogenic Germline Variants in Multiple Myeloma Patients."

• KL2 award through the Clinical and Translational Science Awards (CTSA) Program, under the National Center for Advancing Translational Sciences. The CTSA Program’s KL2 awards support mentored research career development for clinical investigators who have recently completed professional training and who are starting basic, translational, and/or clinical research.

• Multiple Myeloma Research Foundation Research Fellows Award, which supports researchers at the post-doctorate, medical fellow, or junior faculty levels working with a research mentor in the field of multiple myeloma.

Richard Bakst, MD, and Eric Genden, MD, are Principal Investigators on an innovative clinical trial aimed at characterizing and investigating the role of the microbiome in the development of oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous cell carcinoma (OCSCC). "The Role of the Microbiome in Mediating Oral Cavity and Oropharyngeal Cancer Development and Treatment Related Toxicity" will also examine how the oral microbiome landscape changes during the course of radiation treatment and determine whether or not the microbiome plays a role in predicting radiation therapy toxicity in patients with OPSCC.  The observational study—the first of its kind in head and neck cancer—will accrue 350 patients over three years, including patients with and without known risk factors for OPSCC and OCSCC, patients with premalignant lesions, and select healthy controls. To date, 50+ patients have been enrolled.  

Search here for cancer clinical trials by disease site/cancer type, investigator, or trial phase.

John Mascarenhas, MD; Marina Kremyanskaya, MD, PhD; Ronald Hoffman, MD; and colleagues

MANIFEST: Pelabresib in combination with ruxolitinib for Janus Kinase inhibitor treatment-naïve myelofibrosis

Journal of Clinical Oncology. 2023 Mar 7. PMID: 36881782



This paper reports on the phase II MANIFEST trial (NCT02158858) of myelofibrosis patients unresponsive to Janus kinase inhibitors (JAKis) treated with pelabresib (an investigational, selective oral bromodomain and extraterminal domain inhibitor) and ruxolitinib. The drug combination was well tolerated and showed durable improvements in spleen and symptom burden, with potential disease-modifying activity as indicated by biomarker findings. It has the potential to improve the standard of care for JAKis treatment-naïve patients with myelofibrosis.

Ananya Mukherjee, PhD; Jose Javier Bravo-Cordero, PhD

Regulation of dormancy during tumor dissemination: the role of the ECM

Cancer Metastasis Reviews. 2023 Feb 21. PMID: 36802311

This review focuses on the biology of disseminated tumor cells, their invasive nature, how they reach distant organs, and their link to dormancy programs. It also discusses the importance of niches in which DTCs reside and the role of the extracellular matrix in sustaining dormant niches at distant sites. Understanding the dormancy niche and how migratory and dormancy programs are regulated in DTCs will inform new therapeutic targets.

Tizita Zeleke, PhD; Jose Silva, PhD; and colleagues

Network-based assessment of HDAC6 activity predicts preclinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer

Nature Cancer. 2023 Feb. PMID: 36585452



Based on preclinical studies demonstrating that the sensitivity to the leading HDAC6 inhibitor ricolinostat can be predicted by a computational network-based algorithm (HDAC6 score), Dr. Silva and colleagues designed a phase 1b dose-escalation clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in patients with metastatic breast cancer. Findings showed that the two agents can be safely combined. Results also indicated clinical activity in patients with HR+/HER2- breast cancer and the potential of using the HDAC6 score as a predictive biomarker.

Christian Rolfo, MD, and colleagues

NPY methylated ctDNA is a promising biomarker for treatment response monitoring in metastatic colorectal cancer

Clinical Cancer Research. 2023 Jan 30. PMID: 36716292



Dr. Rolfo and colleagues studied the value of analyzing methylation markers in liquid biopsies to monitor patients with metastatic colorectal cancer (mCRC) in the PANIB trial, a phase II trial comparing FOLFOX plus panitumumab and FOLFOX plus bevacizumab in patients with RAS wild-type unresectable mCRC.  Findings confirm that baseline methylated circulating tumor DNA (ctDNA) is a prognostic marker. In addition, results indicate that analysis of methylated ctDNA of sequentially collected liquid biopsies can be used for the follow-up of patients with mCRC.

Monday, May 22, 9 am-5 pm

Davis Auditorium, The Leon and Norma Hess Center for Science and Medicine

Organizers: Poulikos Poulikakos, PhD; Alexa Iliana Zaromytidou, PhD, Chief Editor, Nature Cancer

Keynote Speaker: Shiva Malek, PhD, Novartis Institutes for BioMedical Research

More Information/Register/Submit an Abstract

Nina Bickell, MD, MPH, gave an invited talk—“Disparities in Breast Cancer Diagnosis and Management”—at the NCCN 2023 Breast Congress of the National Comprehensive Cancer Network on February 3. 

Jerry Edward Chipuk, PhD, presented a Keynote Lecture at the International Symposium on Mitochondria, Cell Death, and Human Diseases hosted by Jawaharlal Nehru University in New Delhi, India, February 18-19. The title of his presentation was “Mitochondrial Contributions to Cancer: Causes, Consequences, & Coincidence.” 

Ramon Parsons, MD, PhD, and Cardinale Smith, MD, PhD, presented “Confronting Cancer: What Advances are Being Made in Research and Care?" at the 92nd Street Y on January 18. They noted tremendous progress in deciphering cancer biology and developing targeted treatments, as well as challenges related to resistance to treatments, early cancer screening, and equitable distribution of cancer care.



Read More

Recorded Presentation

Upcoming TCI Seminar Series Presentations

March 14, Noon, Davis Auditorium

Maria G. Castro, PhD, University of Michigan

"Epigenetic Remodeling in Gliomas: Impact of DNA Repair and the Tumor Microenvironment"

March 21, Noon, Davis Auditorium

Kimberly Stegmaier, MD, Dana-Farber Cancer Institute

"Targeting Fusion-Driven Cancers"

Request for Abstracts

Researchers who will be presenting at the American Association for Cancer Research (AACR) annual meeting in April are asked to share abstract title and presentation information in this Google doc to enable promotion according to AACR’s embargo policies via social media and in the press. Questions? Contact Marlene Naanes, Director of Media.

Matt Galsky, MD, Chair

Venue and Faculty: TBA

Register

The first annual Pre- and Post-Doctoral Scientific Symposium—a joint effort of The Tisch Cancer Institute (TCI) and the Herbert Irving Comprehensive Cancer Center (HICCC), organized by Janice Gabrilove, MD, and Sandra Ryeom, PhD—was held on February 27 at HICCC. Designed to foster collaboration and scientific exchange, the symposium featured presentations reflective of each of the TCI and HICCC Scientific Programs by postdoctoral scientists and recently-appointed research faculty. Representing TCI were:

• Christos Adamopoulos, PhD (Cancer Clinical Investigation)
• Christina Wang, MD (Cancer Prevention and Control)
• Shuang Wang, PhD (Cancer Mechanisms)
• Pauline Hamon, PhD (Cancer Immunology)

In addition to sharing their impactful work, they addressed the relevance of their research to the cancer burden in Mount Sinai’s catchment areas.

Following opening comments by Ramon Parsons, MD, PhD, and Anil Rustgi, MD (Director of HICCC), Keynote Speaker Justin Xavier Moore, PhD, MPH, Assistant Professor of Medicine and Population Health Sciences at Medical College of Georgia at Augusta University, gave a talk titled “Systemic Discrimination Matters: Exploring the Risk of Cancer Mortality from Chronic Physiological Stress Among Racial and Sexual Orientation Minorities.” Dr. Moore, a cancer epidemiologist, is a former recipient of the American Association for Cancer Research Minority in Cancer Research Award.

A poster session highlighted research from both TCI and HICCC; two poster winners from each institution received cash prizes of $250. Winners from TCI:

• Magdalena Żak, PhD (third from left in photo below)
• Sweta Sudhir, MD student (fifth from left in photo below)