More than 50 years after the United States formally declared war on cancer, what is the prognosis for innovative cancer research and care?

Two Mount Sinai leaders in cancer care and research, Ramon Parsons, MD, PhD, Director of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and Cardinale Smith, MD, PhD, Vice President, Cancer Clinical Services for the Mount Sinai Health System, offered their perspectives as part of a recent 92nd Street Y online event. You can watch the video here.

The two agreed on this overarching message: Tremendous progress has been made in unraveling the complex biology of cancer and targeting its many forms with advanced new medicines, particularly immunotherapies. But looming just as large are the challenges that remain in areas like overcoming resistance to these medicines, early detection of cancer through screening, and ensuring the equitable distribution of cancer care to diverse and disadvantaged populations.

Ramon Parsons, MD, PhD

“After 50 years we have a much more sophisticated understanding of how genes are altered in the cancer cell and how cancer cells reprogram the tumor microenvironment,” said Dr. Parsons, the Ward-Coleman Chair in Cancer Research. “And that has pushed the envelope in terms of our knowledge of the biology of cancer and, just as importantly, how we treat it. We’re seeing better outcomes for more and more of our patients and believe cancer rates will continue to come down because of treatments we didn’t have in the past, and more informed prevention.”

Dr. Smith, who is also Chief Medical Officer for the Tisch Cancer Hospital and a Professor of Medicine (Hematology and Medical Oncology), described the dramatic changes in cancer care and treatment, particularly in her specialized field of lung cancer.

“When I finished my fellowship training 12 years ago we had just two drugs for lung cancer, and now there are so many more,” she said. “Patients I treated as a fellow are still alive today thanks to clinical trials for new investigative drugs they were able to enroll in.”

Immunotherapies have carved out many of the greatest gains, while also raising some obstacles for the research community. Immunotherapy refers to treatments that use a person’s own immune system to fight cancer.

“The next frontier is determining which patients are going to have a long-term response to immunotherapy, and how do we overcome the resistance we so often see with these therapies,” said Dr. Parsons. “That’s the biology we still need to figure out, and to that end some of the research we’re most excited about is aimed at helping us better understand the switches in the immune system and how they can be regulated therapeutically.”

Two other areas of research where Dr. Parsons sees great promise are tumor suppressors, which are genes that regulate a cell during cell division, and liquid biopsies, which can detect through a simple blood test at the doctor’s office circulating tumor cells and tumor DNA.

With a strong background in tumor suppressors, he sees great advantage in being able to develop gene therapy or other innovative approaches to restore tumor suppressors, a natural part of the body’s defense mechanism that becomes altered or mutated in almost every type of cancer.

Liquid biopsies, still in early-stage development, could be another significant development. “This idea of being able to catch cancers before they are recognizable is going to ultimately move the needle in improving patient survival,” he said.

Cardinale Smith, MD, PhD

For Dr. Smith, early detection includes more aggressive screening by the health care providers.

“Uptake of lung cancer screening has been slow,” she said. “A lot of the work we’ve been doing at Mount Sinai is connecting with the community to understand what their needs are and how they prefer to partner with us. As a result, we’ve increased mammographies for women to detect breast cancer, and improved colorectal cancer screening for both men and women. Now we need to make the same kind of progress with lung cancer screening.”

She noted that as part of its outreach, Mount Sinai in April 2022 launched the Mount Sinai Robert F. Smith Mobile Prostate Cancer Screening Unit after noticing a high mortality rate for the disease in certain neighborhoods of New York City with a high Black male population. The purchase was funded by a $3.8 million donation from philanthropist Robert F. Smith. This successful effort between the Institute and the Department of Urology has been collecting blood samples to measure PSA levels and referring individuals for follow-up care when a problem is detected.

The nation’s war on cancer formally began with the National Cancer Act of 1971, which established the National Cancer Institute. As for the future of cancer care, Dr. Smith foresees patient care navigation and a palliative care workforce as movements with transformative potential.

Navigators with the ability to compassionately guide people through the often challenging cancer screening and treatment process would be an extremely beneficial allocation of resources, she maintains. So would development of specialized palliative care teams that could provide training and skills to oncologists and other clinicians, including nurses and advanced practice providers.

“We know that palliative care when combined with standard oncologic care can improve patients’ quality of life and mood by decreasing depression,” she said. “It also decreases unnecessary utilization of acute care, such as emergency room visits, hospitalizations, and readmission. Most importantly, it aligns cancer care with the goals and values of the patients, which all of us as clinicians need to hold as sacred in the years ahead.”

Erik Lium, PhD, Executive Vice President, Mount Sinai Innovation Partners, left, presents the Mount Sinai Inventor of the Year Award to Steven J. Burakoff, MD.

Individuals and teams from the Mount Sinai Health System were honored for significant advances in biomedical research, technology, and medicine at the eighth annual Mount Sinai Innovation Awards ceremony held Monday, October 24.

Through the dedication of presenters, participants, attendees, and event organizers, the Innovation Awards showcase and inspire ingenuity and advances in research, technology, medicine, and health care.

Steven J. Burakoff, MD, Dean for Cancer Innovation and Lillian and Henry M. Stratton Professor of Cancer Medicine at the Icahn School of Medicine at Mount Sinai, received the Mount Sinai Inventor of the Year Award for developing small molecule therapeutic inhibitors targeting HPK1 to regulate the immune response against cancer. This technology entered phase 1 clinical trials in spring 2022. The award recognizes individual or collaborative investigators in the Mount Sinai Health System whose research is making, or has the potential to make, significant positive and product-driven impacts on health.

The Mount Sinai Transaction of the Year Award was given to Manish Arora, PhD, BDS, MPH, Professor and Vice Chairman; Christine Austin, PhD, Associate Professor; and Paul Curtin, PhD, Associate Professor, all at the Department of Environmental Medicine and Public Health. They are co-founders of Linus Biotechnology, which aims to develop and commercialize a novel precision exposome sequencing platform for complex diseases. The company received Breakthrough Device designation from the U.S. Food and Drug Administration for StrandDx™-ASD, a diagnostic aid for autism spectrum disorder. The award recognizes a notable technology from the Mount Sinai Health System that represents a major breakthrough in research and a strong commercial partnership for advancement,

The Lifetime Achievement Award was given to Robert J. Desnick, MD, PhD, Chair Emeritus and Professor, Genetics and Genomic Sciences, whose research led to the development of Fabrazyme® and GIVLAARI®, drugs for treating lysosomal storage disease. He co-founded Amicus Therapeutics, a company that aims to develop and deliver medicines for rare metabolic conditions, including olipudase alfa.

Scott Friedman, MD, Dean for Therapeutic Discovery, served as host of the event.

The Mount Sinai Pitch Challenge Award was given to Tyree Williams, MEng, a biomedical engineering doctoral researcher at Rensselaer Polytechnic Institute and a visiting graduate student researcher at Sinai BioDesign.  He is the founder of Kratos Orthopedics, which is developing a novel mortar bone cement system to improve mechanical responses and post-operative care in patients who have undergone spinal surgeries. The award is the capstone event for Mount Sinai Innovation Partner’s Entrepreneurship Program, where finalists compete for a cash prize and pro-bono services to continue the development of health care solutions.

The Faculty Idea Prize was given to Sairam Geethanath, PhD, Assistant Professor, Diagnostic, Molecular and Interventional Radiology, and Shilpa R. Taufique, PhD, Assistant Professor, Psychiatry, for their work on substance use disorders, which affect brain health, especially in underserved populations, due to inequitable health care access. The award aims to support a collaborative, innovative, research idea by junior faculty that can potentially be translated into a marketable product through the development of therapeutics, devices, diagnostics, digital health applications, and/or data driven educational or community-based interventions.

The KiiLN Postdoctoral Entrepreneurship Award was given to Joon Ho Seo, PhD, a postdoctoral fellow, and SmartMazes, LLC. This project is focused on designing and manufacturing economical, modular, and modifiable rodent behavioral apparatuses that can serve as multiple mazes for the purpose of basic and translational neuroscience. The award is designed to highlight entrepreneurial endeavors of Mount Sinai postdoctoral fellows who co-found or lead companies by advancing their discoveries beyond the bench to create diagnostics, devices, and therapeutic products or by applying other solutions, in order to address unmet needs in life sciences.

The i3 Prism Award was given to Benjamin Rodriguez, a medical student, and Maddison Archer and Emelie Lassen, PhD, both postdoctoral fellows. The Mount Sinai i3 Prism technology commercialization fund aims to bring new health care solutions to patients and society by advancing technologies from women and Black, indigenous and people of color (BIPOC) inventors closer to the marketplace.

The i3 Genesis Award aims to translate Mount Sinai discoveries in various health care fields with clear potential for commercialization and defined technology or data gaps that can be addressed with funding. It was given to six teams for 2022 and five teams for 2021. The 2022 recipients are:

• Daniela Sia, PhD, Anna Tocheva, PhD, Elliot Merritt, PhD, and Emily Bramel
• Isabella Morgan, Joshua Bederson, MD, Mitch Baldwin, and Benjamin Rapoport, MD
• Weijia Zhang, PhD, Stephen Ward, MD, Fasika Tedla, MD, Zhengzi Yi, MSc, and Caixia Xi, MSc
• Yulia Landa, PsyD, MS, and Rachel Jespersen, MSW
• Kara Bagot, MD, Angela Diaz, MD, and Anne Nucci, MD
• Margaret Brandwein, MD, and Mark Urken, MD

The 2021 recipients are:

• Alfred-Marc Iloreta, MD, Turner Baker, PhD, Alexis Bruhat, MEng, and Benjamin Rapoport, MD
• Jonathan DePierro, PhD, Laurel Morris, PhD, James Murrough, MD, PhD, Dennis Charney, MD, and Adriana Feder, MD
• Mark Rea, PhD, and Bridget Bradley
• Evren Azeloglu, PhD, Eric Lima, PhD, Alan Benvenisty, MD, Kirk Campbell, MD, and Jacob Wright
• Gautam Kamthan, MD, and Sean Ianchulev, MD

The winners who attended the event held in Davis Auditorium in the Leon and Norma Hess Center for Science and Medicine on the Icahn School of Medicine at Mount Sinai campus.

The Diversity Innovation Hub Innovator Prize was given to Tanvir Islam, founder and CEO of TYCA, who has been supporting the growth of local economies and accessibility of resources within communities.

The Diversity Innovation Hub Founders Award was given to Gil Addo, MBA, cofounder and CEO of RubiconMD, who has been transforming the delivery of digital health through making specialty consults more accessible to all populations.

The THRIVE Fellowship Award was given to these teams:

• Spinovations: Tyree Williams, MEng, Ian Odland, BS, Eugene Hrabarchuck, BA, Zaara Irshad, MHA, and Janvi Patel, BA (mentor: Tanvir Choudhri, MD). Spinovations is working on developing a new spinal screwdriver for more patient-centered, minimally invasive surgeries.
• ai: Faris Gulamali, BS (mentor: Neha Dangayach, MD). They are focusing on the problem of monitoring intracranial pressure.

• Metaphor: Hyomin Seo, BEng, and Brian Soong, BA (mentors: Towfique Raj, PhD, John Doucette, PhD, and Emma Benn, DrPH). Metaphor is working on an AI-based project to detect early signs of Alzheimer’s disease in the speech patterns of non-English speakers.

• SSI Detection: Jenny Chen, BS, Nasseef Quasim, MDc, Sushruta Iruvanti, BA, Vivian Utti, BS, and Vivek Prakash, MD. They are working on a system to detect early signs of surgical site infection following vascular surgery procedures, using a combination of clinical biomarkers and remote visualization/monitoring technologies.

The Trainee Innovation Idea Award was given to these individuals:

• MD and MD/PhD Students: Randal A. Serafini, MS, Justin J. Frere, BS, Venetia Zachariou, PhD, and Benjamin R. TenOever, PhD, for developing a pre-clinical hamster model of long COVID for enhanced therapeutic development.

• PhD Students: Pushkala Jayaraman, MS, Justin Kauffman, BS, and Girish Nadkarni, MD, MPH, for work on AI and electronic health records.

• Postdoctoral Fellows: Wontack Han, PhD, Ryan Walker, PhD, Jeremiah Faith, PhD, and Maia Kayal, PhD, for identifying gut microbiome metagenomic features to develop a clinical prediction tool for inflammatory bowel disease.

• House staff: Harry Anastos, MD, for utilizing the expression of immune checkpoint proteins in the peripheral blood of patients with elevated prostatic specific antigen (PSA) to predict the presence of prostate cancer.

The Mount Sinai Innovation Awards hosts are: The office of the Dean; Mount Sinai Innovation Partners; the Office of Faculty Development; the Office for Diversity and Inclusion; the Keystone for Incubating Innovation in Life Sciences Network (KiiLN); ConduITS-Institute for Translational Sciences; Sinai BioDesign; the Department of Medical Education; the Graduate School of Biomedical Sciences; the Graduate Medical Education Office; and the Office of Postdoctoral Affairs.

Louise Malle, MD/PhD candidate, and Dusan Bogunovic, PhD

In April 2020, as the COVID-19 pandemic spread through New York City, Louise Malle, an MD/PhD candidate at the Icahn School of Medicine at Mount Sinai, turned her focus to the disturbing statistics coming out on disease severity. She thought the data might inform her research to better understand immunity in people with Down syndrome.

Louise Malle, MD/PhD candidate

Ms. Malle, who works in the lab of Dusan Bogunovic, PhD,  surveyed thousands of patients diagnosed with COVID-19, and essentially found that individuals with the syndrome have about 10 times the likelihood of having extremely severe disease.

Dr. Bogunovic is Professor at the Marc and Jennifer Lipschultz Precision Immunology Institute, The Mindich Child Health and Development Institute, the Icahn Genomics Institute, and the departments of Oncological Sciences, Microbiology, Pediatrics, and Dermatology, as well as a Director of the Center for Inborn Errors of Immunity—all at Icahn Mount Sinai.

It turns out that Ms. Malle’s epidemiological observation added to a body of literature that suggests that severe viral disease is a problem in Down syndrome. The work led to new findings, published online on October 14, 2022 in the journal Immunity, showing that people with Down syndrome have less frequent but more severe viral infections.

“As we all were caught in the COVID-19 pandemic, Louise saw what was going on in the clinic in people with Down syndrome (based on her review of hospital records),” said Dr. Bogunovic, senior study author. “She saw what was going on in the world and then came to the lab, ultimately figuring out, at least in part, why this understudied and underserved population experiences more severe viral infections across the board.”

According to the study, this phenomenon is caused by increased expression of genes that sense an antiviral cytokine, type I interferon (IFN-I), as they are encoded on chromosome 21. Elevated sensing of IFN-I lead to hyperactivity of the immune response initially, but the body overcorrects for this to reduce inflammation, leading to increased vulnerability later in the viral attack.

Dusan Bogunovic, PhD

“Usually too much inflammation means autoimmune disease, and immune suppression usually means susceptibility to infections,” says Dr. Bogunovic. “What is unusual is that individuals with Down syndrome are both inflamed and immunosuppressed, a paradox of sorts. Here, we discovered how this is possible.”

Down syndrome is typically caused by triplication of chromosome 21. The syndrome affects multiple organ systems, causing a mixed clinical presentation that includes varying degrees of intellectual disability, developmental delays, congenital heart and gastrointestinal abnormalities, and Alzheimer’s disease in older individuals. It is universally present across racial, gender, or socioeconomic lines in approximately 1 in 800 live births, although there is considerable variation worldwide.

Recently, it has become clear that atypical antiviral responses are another important feature of Down syndrome. Increased rates of hospitalization of people with the genetic disorder have been documented for influenza A virus, respiratory syncytial virus, and severe acute respiratory syndrome due to coronavirus (SARS-CoV-2) infections, according to the researchers.

“We have a lot more to do to completely understand the complexities of the immune system in Down syndrome,” said Ms. Malle, first author of the study. “We have here, in part, explained the susceptibility to severe viral disease, but this is only the tip of the iceberg.”