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.”

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.”

Valentin Fuster, MD, PhD, at the European Society of Cardiology Congress in Barcelona, Spain

In a milestone in cardiovascular medicine, a  three-drug medication known as a “polypill” was found effective in preventing adverse events such as heart attacks or stroke in people who have previously had a heart attack, reducing cardiovascular mortality by 33 percent in this patient population. These are findings from the SECURE trial led by Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital.

The study results were announced on Friday, August 26, at the European Society of Cardiology Congress (ESC 2022) in Barcelona, Spain, and published in The New England Journal of Medicine.

“The results of the SECURE study show that for the first time that the polypill, which contains aspirin, ramipril, and atorvastatin, achieves clinically relevant reductions in the recurrent cardiovascular events among people who have recovered from a previous heart attack because of better adherence to this simplified approach with a simple polypill, rather than taking them separately as conventional,” says Dr. Fuster, General Director of the Spanish National Center for Cardiovascular Research (CNIC), which developed the polypill.

Patients recovering from a heart attack—also known as myocardial infarction—are prescribed specific treatments to prevent subsequent cardiovascular events. Standard therapy includes three different drugs: an antiplatelet agent (like aspirin); ramipril or a similar drug to control blood pressure; and a lipid-reducing drug, such as a statin. However, fewer than 50 percent of patients consistently adhere to their medication regimen.

“Although most patients initially adhere to treatment after an acute event such as an infarction, adherence drops off after the first few months. Our goal was to have an impact right from the start, and most of the patients in the study began taking a simple polypill in the first week after having a heart attack,” Dr. Fuster explains.

“Adherence to treatment after an acute myocardial infarction is essential for effective secondary prevention,” says José María Castellano, MD, study first author and Scientific Director of Fundación de Investigación HM Hospitales.

The concept of a polypill for cardiovascular disease prevention was proposed in 2003 and widely debated among experts, with some arguing that it could reduce heart disease at a population level and others arguing that patients could wrongly consider it as a substitute for healthy lifestyles. In 2007, the potential value of applying the polypill strategy in high-risk patients was recognized by the WHO and the World Heart Federation, and Dr. Fuster authored a call to action in Nature Clinical Practice Cardiovascular Medicine,  “A polypill for secondary prevention: time to move from intellectual debate to action.”

Scientists at the CNIC, in partnership with FERRER laboratories, developed a polypill and have conducted a range of studies over the intervening years. CNIC scientists first demonstrated that prescription of the CNIC polypill significantly improved treatment adherence among patients recovering after a myocardial infarction, in the FOCUS study, published in the Journal of the American College of Cardiology (JACC).

The CNIC team launched the SECURE study, an international randomized clinical trial, to determine whether the improved treatment adherence with the polypill translated into a reduction in cardiovascular events. The polypill analyzed in the study, commercialized under the name Trinomia, contains aspirin (100 mg), the angiotensin-converting enzyme inhibitor ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg).

SECURE included 2,499 patients from seven European countries (Spain, Italy, Germany, the Czech Republic, France, Poland, and Hungary) recovering after a heart attack. Study participants were randomly assigned to receive standard therapy or the CNIC polypill. The average age of the participants was 76 years, and 31 percent were women. The study population included 77.9 percent with hypertension, 57.4 percent with diabetes, and 51.3 percent with a history of smoking tobacco.

Researchers analyzed the incidence of four major cardiovascular events: death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, and need for emergency coronary revascularization (the restoration of blood flow through a blocked coronary artery). The study followed patients for an average of three years and produced conclusive results: patients taking the CNIC polypills had a 24 percent lower risk of these four events than patients taking the three separate drugs.

The standout finding of the study is the effect of the polypill on the key outcome of cardiovascular-related death, which showed a relative reduction of 33 percent, from 71 patients in the group receiving standard treatment to just 48 in the polypill group. Importantly, the study found that patients in the polypill group had a higher level of treatment adherence than those in the control group, thus confirming the findings of the earlier FOCUS study, and in part such good adherence appears to explain the benefits of the simple polypill.

“The SECURE study findings suggest that the polypill could become an integral element of strategies to prevent recurrent cardiovascular events in patients who have had a heart attack,” Dr. Fuster says. “By simplifying treatment and improving adherence, this approach has the potential to reduce the risk of recurrent cardiovascular disease and death on a global scale.”