Covid sparks talk on new thinking for a new cancer moonshot

For over a century, clinicians have been trained to define and treat conditions they can see, which is why they classify tumours according to where in the body they are found



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By Daniel J. Arbess

Published: Tue 1 Mar 2022, 12:11 AM

US President Joe Biden’s recently announced goal of reducing America’s cancer death rate by half in the next 25 years, with its encouraging emphasis on early detection and prevention, sounds bold. But we can do even more to tackle the disease — and faster.

That is because scientific advances over the past decade have given us the tools to move from fighting cancerous tumours to identifying and intercepting the biological mechanisms that cause them.

The problem is that prevention and wellness are not yet reimbursed in a healthcare system designed to manage symptoms.

We, therefore, need a new cancer moonshot to adapt our mindsets and institutions to the new science, as we did after the Covid-19 pandemic erupted.

For over a century, clinicians have been trained to define and treat conditions they can see, which is why they classify tumours according to where in the body they are found. But what if the damage causing the tumour occurs somewhere else?

The reason cancers frequently return after resection, radiation, and chemotherapy might be that tumours are not the fundamental problem. Rather, they are the terminal symptoms of a so-called genetic insult, which triggers a cascade of cellular dysfunction that progresses for months or years before tumours appear. We have learned this in recent years by decoding the human genome and progressively understanding the function of different genes, specifically the effect of their mistranscription on proteins and other key elements of cellular chemistry.

These tools allow us to “see” the causes of cancers at their molecular point of impact. The process starts with genetic damage, which is sometimes “germline”, or inherited, and sometimes triggered by “epigenetics” such as environmental toxins, an unhealthy diet, or other lifestyle choices. Both types of damage are further influenced by age, ethnicity, and other factors, all of which comprise an individual’s biological constitution, or deep phenotype.

Cancers emerge when our native immune system fails. Genetic mutations occur for everyone millions of times every day, and our immune system addresses them. The question is why some people experience an uncontrolled proliferation of mutated cells.

While every person’s immune response is affected by their unique deep phenotype, we know that aging is a factor. The immune system has evolved over billions of years and has its own pace of adapting to the rapidly emerging new toxins and lifestyles of industrial and post-industrial societies. This suggests that, as we age, we accumulate more genetic insults and therefore a greater risk of cancer and other biological conditions.

Modern technologies, by enabling us to focus on an individual patient’s molecular history, provide an opportunity to write the definitive chapter of the war on cancer. The goal should be to understand how the disease uniquely emerges in each patient’s biological constitution, and how deep phenotypical characteristics change it.

This is possible today because new objective measurement tools enable scientists to track people’s biological makeup far earlier and more accurately than they could by relying on scans. For example, biosensors can capture a patient’s experience outside the physical boundaries of health-care institutions. And artificial intelligence can detect signs of trouble by longitudinally observing vast and diverse biological data emerging from modern sequencing and imaging technologies.

The fact that cancer evolves and expresses itself differently in each individual case has enormous implications for the process of approving new therapies. Today, this involves long, slow trials involving large cohorts of patients with similar end-stage symptoms. But in the new phase of the war on cancer, we will build solutions from single successful outcomes to broader populations that share key deep-phenotype characteristics.

The healthcare system is not adapting quickly enough — yet. One encouraging outcome of the Covid-19 pandemic is that the US Food and Drug Administration, the regulatory gatekeeper of evolving science, has shown greater willingness to accelerate new approaches. And big pharmaceutical firms are realizing that they don’t necessarily need new drugs, but instead a better understanding of what is happening to patients, and targeted combinations of interventions addressing each individual’s biology. Researchers and clinicians will catch up when insurance companies and national programs eventually start paying for deep-phenotype testing and analysis.

The pandemic demonstrated that new technologies can help to solve big health problems fast. Specifically, we know that the human immune system can be programmed and stimulated to attack potentially harmful molecular changes long before they cascade into visible symptoms.

Likewise, we must now reinvent how we detect cancer. If we can target aberrant microscopic processes, we can intercept them. And if we can intercept them, we can eventually preempt and prevent them, thus extending people’s healthy life span. That would transform our current system of symptom management into real health care — for cancer and many other unsolved health challenges. — Project Syndicate

Daniel J. Arbess, CEO of Xerion Investments and founder of Xerion Precision Biosciences, is a member of the Council on Foreign Relations and serves on the boards of Cancer Expert Now and the Global Virus Network.