Applied Molecular Medicine Signals the Future of Personalized, Preventive Cancer Care

In Partnership With:

Partner | Cancer Centers | <b>John Theurer Cancer Center, Hackensack University Medical Center</b>

Andre Goy, MD, discusses advances in the field of oncology that prompted the development of the Hennessy Institute, how early cancer detection can improve patient outcomes, and the importance of employing accessible cancer prevention strategies.

Using precision medicine, leveraging immunotherapy, and measuring patient outcomes are hallmarks of the drive to improve cancer care that the Hennessy Institute for Cancer Prevention and Applied Molecular Medicine aims to implement and expand upon to reduce the incidence and severity of cancer, according to Andre Goy, MD.

In March 2023, the Hackensack Meridian John Theurer Cancer Center announced plans to establish the Hennessy Institute with a grant from the Mike & Patti Hennessy Foundation. This institute will focus on helping patients understand their risk for developing cancer, educating patients about preventive lifestyle changes, and providing patients with multidisciplinary treatment resources throughout their individual disease courses.

“We will reduce the burden of cancer at the Hennessey Institute through early detection, risk mitigation in the pre-cancer setting, and reducing the recurrence of cancer post-treatment,” Goy said in an interview with OncLive®.

In the interview, Goy discussed advances in the field of oncology that prompted the development of the Hennessy Institute, how early cancer detection can improve patient outcomes, and the importance of employing accessible cancer prevention strategies.

Goy is physician in chief of Hackensack Meridian Health Oncology Care Transformation Services, and chairman, chief physician officer, and chief of the Lymphoma Division at John Theurer Cancer Center at Hackensack University Medical Center in New Jersey.

OncLive®: What is the significance of establishing the Hennessy Institute?

Goy: We’re fortunate that there is an unprecedented revolution happening in medicine, particularly in cancer, [consisting of 3 advances]. Now, precision medicine is becoming a reality, immunotherapy is becoming its own modality of cancer therapy, and data analytics will help us measure and improve the outcomes of patients.

There are 2 important questions in medicine and in oncology to answer, and only 2 questions that matter. The first one is: What’s my best option now for any given patient, given the complexity of the landscape and the number of options? The second one is: What’s the best sequence of care? Because we have so many options, we want [use what will give patients] the longest mileage, so they have the longest benefit and the best outcome. That’s a way to remove the variance of care and control costs at the level of the population.

However, the future of cancer is as much diagnostic as it is therapeutic because we clearly have a growing awareness of the diversity of cancer as a collection of hundreds of different diseases [that are] not just organ-based, but [based on] molecular features. This diagnostic revolution is becoming a reality thanks to next-generation sequencing [NGS], which is possible in routine care at the bedside. NGS allows us, from liquid biopsies or on the tissue, to better identify what’s driving the tumors [and see the] somatic mutations and abnormalities that are driving the cancer cells, therefore giving us a better picture of the underlying cancer cell biology for a given patient. [We can use NGS] to try to identify the best [treatment] options and use precision medicine to treat cancer.

However, the next step is looking at the broader picture because cancer will increase in incidence by 60% or 70% in the next 25 years. Two-thirds of cancer diagnoses and deaths have no screening tests. That’s an issue. If you diagnose a cancer earlier, the outcome is better. The big killers, pancreas cancer, lung cancer, and ovarian cancer, are often diagnosed late, and the survival at 5 years is 5% to 10% in advanced-stage disease vs 85% to 90% in early-stage disease.

If we use molecular diagnostics to try to move beyond cancer as [just 1] disease, [we can do pre-cancer care] to diagnose patients early or mitigate the risk of cancer for a patient with, for example, BRCA1 and BRCA2 [mutations]. We can use technology, molecular diagnostics, and applied molecular medicine to diagnose cancer earlier. [For example, the way we currently monitor a patient with] a history of heavy smoking is to look at a lung nodule that is growing on repeat imaging. If we can pair this with molecular diagnostics, we can likely diagnose [their cancer] earlier.

The other aspect of applied molecular medicine is in post-cancer care. [Regarding] minimal residual disease [MRD], if a patient is in remission by PET scan and all other testing after chemotherapy, we monitor them with repeat imaging and bloodwork. However, we know now that almost all patients who are in complete remission but are MRD positive relapse. The next step is to have a new end point, MRD negativity. That’s applied molecular medicine. We use liquid biopsies to explore giving additional treatment as consolidation to prevent recurrence.

The Hennessy Institute will focus on applying molecular medicine mostly as pre-cancer [care], but also as post-cancer care as well, to expand the scope of treatment and reduce the burden of cancer in the population.

What cancer prevention and screening strategies does the Hennessy Institute plan to implement?

In cancer screening, there are multiple situations. There’s either the patient who has a germline risk factor like BRCA1 or BRCA2 mutations, although now the list includes over 100 genes associated with an increased risk of cancer, or patients with a family history of cancer. With many family histories of cancer, there is additional risk. These patients are ‘well and worried.’ They don’t have cancer, but they have a significant family history. These patients want to know if they have an early cancer, and the patients who have a germline risk factor want to know what they can do to reduce their germline risk factor. Sometimes [patients can implement preventive] lifestyle changes, or [we may use] molecular monitoring in the future to see if we can identify [risk factors] earlier. That’s the screening situation.

In the real world, the way the Hennessy Institute will work is that, after [educating patients about this new resource], patients will call because they have a history of cancer, they’re worried they could have cancer, or they have risk factors [like] obesity and heavy smoking. These patients [will be taken in remotely by our] navigator online, and then [we will] evaluate their risk factors and do liquid biopsies to try to identify potential risk markers. That will all be done in innovation clinical trials to make sure we improve [cancer] detection and the outcomes of these patients. If these patients have an abnormality, they will get imaging, and if they don’t, they will be repeatedly monitored over time.

For example, in lung cancer, patients who are heavy smokers have a higher incidence of lung cancer, and 75% of lung cancers present at an advanced stage. The way we screen patients now, only 3% of the population at risk of lung cancer is screened by low-resolution CAT scan that is repeated over time when a nodule is growing to [help us] decide if we should go after that nodule. If we can pair imaging and molecular testing, this will be [more effective] than just monitoring over time, [which often makes patients] more worried instead of reassured. If we can do [molecular testing], we will increase our capacity for detecting the nodules we can just monitor vs the nodules we should go after immediately. This will have a real effect, and that’s where the future of medicine is going. The large cancer programs are all heading in that direction as the next stepping stone.

In general, not just in cancer, there’s a move in medicine to go from symptom management of the disease to preemptive medicine, [including] early diagnosis, risk mitigation, and lifestyle changes. [A total of] 50% of cancers are preventable by lifestyle changes. [With these] screening tools and screening technologies, we will also engage patients in changing their lifestyles to reduce their risk of developing cancer.

How will the Hennessy Institute address inequities in cancer research and prevention and work to close cancer screening gaps and alleviate the financial burden of preventive care in underserved communities?

Access to innovation, clinical trials, care, and screening is a major issue in our country and across the world. We are in communities with less access to screening technologies [and where] patients [often present with] more advanced diagnoses. Innovation is a way to leapfrog into the future to improve access to care and reduce inequity.

[For example, smoking] is often more predominant in the communities most at risk [for cancer and least likely to] go to screening. If we make [screening] easier, more user-friendly, and [able to provide more technologically advanced] and better results [that show its] benefits, more patients may get screened.

This is not complicated to do, because [screening involves] a liquid biopsy that can be done with a blood test. We can engage the community and probably also use our medical students at the Hackensack Meridian School of Medicine, who are paired with families in inner cities, to explain to patients the potential of early diagnosis. This will take a bit of a learning curve, but in the future, patients will try to find a way to detect cancer earlier.

There’s also the situation of a patient who had early cancer, [detected by a] mammogram [or other] routine screening, had surgery, and who, after lung cancer resection, for example, is told [that resection has] potential curative intent, meaning they are cured by their surgery. When we look at the cell-free DNA by liquid biopsy in those patients, we’ll be able to identify the ones who will relapse. If a patient’s cell-free DNA is negative after surgery, [they have a] minimal chance of relapse. If a patient is cell-free DNA–positive after surgery, they have almost a 100% chance of relapse and dying from their disease. [Determining patients’ cell-free DNA status] will be important.

Overall, what is the main goal of the Hennessy Institute?

[The main aim is] to use technology to accelerate early detection and risk mitigation, so we can engage patients in lifestyle changes and reassure them that we can detect cancer earlier. Importantly, there are other [diseases] we can detect with liquid biopsies, [such as] clonal hematopoiesis of indeterminate potential [CHIP], which transforms into acute myeloid leukemia in 2% of patients. [Although] that’s not a [big] risk, patients with CHIP have a 40% increased chance of having a stroke or cardiac event. These patients could be preemptively referred to cardiologists to prevent [their disease from] evolving. [We need to make this process] user friendly, so patients do it.

On the post-cancer side, [we want to] reduce the burden of cancer relapse by managing MRD preemptively and preventing disease recurrence. We are thankful to be given this opportunity by the Hennessy family and are looking forward to working together.

[We want to make cancer care] user friendly and less disruptive. No patient wants to know they have a gene that puts them at risk [for cancer] and be worried and disrupted in their life, [needing to] take [time] off from work, [for example], to get repeat testing. [This care needs to be] as patient focused as possible in their ecosystem at home, not in a hospital. The future is not about bricks and mortars, the future is about clicks and mortars.

Reducing the burden of cancer is part of our mission, by helping every patient and by [preemptively treating] several new cancers or detecting them earlier so [patients] have better outcomes.