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Precision medicine: From one-size-fits-all to personalized healthcare

Scientist pipetteAdvances in technology are essential if precision medicine is going to become reality.

Imagine a future in which, rather than using symptoms to identify a disease, your genes, metabolism, and gut microbiome inform how your individual health is managed. This is the vision of precision medicine.

Traditional medicine uses symptoms to diagnose diseases, and drugs to treat these symptoms. But precision medicine aims to turn this concept on its head.

By identifying the factors that predispose a person to a particular disease and the molecular mechanisms that cause the condition, treatment and prevention strategies can be tailored to each individual. 

So, how do we get from traditional to precision medicine? Advances in genetics and molecular analysis techniques have been a deciding factor, as has getting patients involved with managing their own health.

However, is precision medicine going to revolutionize how we treat all medical conditions, or will it be the privilege of a select few?

Innovation drives precision medicine

To the National Institutes of Health (NIH), “[P]recision medicine is a revolutionary approach for disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology.”

Launched by President Barack Obama in 2015, the Precision Medicine Initiative “will pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.”

Breakthroughs in molecular biology have been key to getting precision medicine off the ground.

Next-generation DNA sequencing is now routinely used to identify genetic mutations that drive specific cancers, and biomarkers that predict disease risk or how well a person will respond to a particular treatment are increasingly becoming reality in medical practice.

Cancer is the one area wherein precision medicine seems to be making significant headway. New therapies seek to target the specific cellular pathway that is being exploited by a cancer, with the view to making short the life of the tumor.

This approach is already being employed in clinical trials to treat patients with melanoma who have a mutation in the BRAF gene, as Medical News Today reported recently.

Precision medicine in cancer

Last week, a study by Dr. Shumei Kato — an assistant clinical professor at the Center for Personalized Cancer Therapy and Division of Hematology and Oncology at the University of California, San Diego Moores Cancer Center — used this approach in 40 patients with rare tumors.

Rare tumors are classed as those that occur in fewer than 15 patients per 100,000 each year, Dr. Kato explains in the paper. While each type of rare cancer might only be shared by a few individuals, overall, 22–25 percent of all adult tumors are rare tumors.

Senior study author Dr. Razelle Kurzrock — a professor of medicine — and Dr. Kato explained to MNT that “patients with rare tumors often have inadequate access to approved drugs or to clinical trials. However, along with the technological advancement, it is now feasible to perform genomic analysis […] as well as protein analysis among patients with rare tumors.” 

Using this approach, the team sought to identify the genetic mutations underpinning each tumor, rather than the clinical classification. This way, they could match 37 of the 40 study participants to a therapy that was either designed for a different cancer or was in the clinical trial stage.

From this group, 21 patients went on to receive a matched treatment and over half went into either partial or complete remission, or their cancer remained stable for at least 6 months.

As Drs. Kurzrock and Kato highlighted:

It was especially important to institute this approach in rare tumors, since there are often so few traditional therapies available to these patients. We were, therefore, filling an unmet need for new treatments for these patients by applying our internal expertise in genomics, immunotherapy, and personalized medicine.”  

The road ahead

Prof. Ze’ev Ronai — chief scientific advisor at the Sanford-Burnham Medical Research Institute in La Jolla, CA — recently commented on the progress that precision medicine has made in the cancer field in an article in the October issue of Trends in Molecular Medicine.

“While at present only a small proportion of cancer patients benefit from targeted therapies,” he explains, “great efforts are ongoing to extend the scope of precision oncology to a broader spectrum of patients.”

Yet, according to Prof. Ronai, looking at genetic mutations alone is not going to be enough if we want to unlock the full potential of precision medicine.

He says that “while genomic profiling provides valuable information regarding genetic mutation […], there are certain inherent limitations of using an approach that simply tests the presence or absence of genetic driver events to inform therapeutic decision-making.”

Some cancers just do not fit into this category, and in such cases, tumors are driven by other factors.

Future precision oncology treatment will need to include the broader landscape of genetic and epigenetic changes that take place in a tumor. Those include the tumor microenvironment, which comprises metabolic as well as immunological changes, in addition to the influence exerted by the microbiome.”

Prof. Ze’ev Ronai

A combination of “omics” analyses is going to be key, Prof. Ronai concludes. This sentiment is echoed by Prof. Michael P. Snyder, who is the director of the Center for Genomics and Personalized Medicine at Stanford University in California.

Combining ‘omics’ in precision medicine

Multi-omics profiling is the analysis of an individual’s genetic makeup (genome) in combination with other factors, such as gene expression (transciptome), proteins (proteome), metabolism (metabolome), and gut microflora (microbiome).

If we want to understand the multiple factors that might influence health and disease, precision medicine must go beyond genetic analysis.

Prof. Snyder says that “by measuring factors beyond the genome and including the environment over time, we can get a detailed portrait of a person’s healthy state and understand what changes when he or she transitions to a disease state.”

In a presentation at the American Society of Human Genetics annual meeting, held in Orlando, FL, last Friday, Prof. Snyder highlighted how he used this approach to study the effects of early intervention strategies to prevent diabetes.

For the study, the team followed 98 people with and seven without prediabetes over the course of 4 years, collecting multi-omics data along the way. According to Prof. Snyder, the results showed that “this portrait really changes from person to person; we all have different molecular profiles.”

However, within the prediabetic group, a clear picture emerged between those sensitive to insulin and those resistant.

“We [found] the insulin resistant folks are dampened in their response to weight gain and other perturbations relative to [those who are] insulin sensitive. Even at baseline they have different molecular and microbial profiles,” Prof. Snyder told MNT.

I want to change medicine. The way we manage health now is Byzantine – it’s typically based on treating patients when they’re sick. By collecting a wealth of information at the individual level about a person’s healthy state, we can identify ways to keep him or her healthy and prevent disease.”

Prof. Michael P. Snyder

The future of medicine

So, does Prof. Snyder see precision medicine entering mainstream medicine in the near future? “Definitely,” he told MNT. “Right now we measure very few things and infrequently.”

But “[i]n the future,” he added, “we will be making many measurements, hundreds if not thousands, every time we sample someone. Many measurements will be continuous using wearable devices.” 

Drs. Kurzrock and Kato agree. “We strongly believe that the precision medicine approach will be routine in the near future. It is already being practiced in certain cancer types,” they said.

Many in the medical and scientific communities clearly see this approach as a game-changer. But change does not always come easily and there are barriers that need to be overcome.

To Drs. Kurzrock and Kato, the barriers lie in the “complexity of the molecular biology of cancer and the paucity of training of physicians in this field.”

“We refer to metastatic tumors as ‘malignant snowflakes,'” they explained, “reflecting the fact that each person’s tumors are both unique and complicated. This means that the traditional one-size-fits-all approach is suboptimal. Treatment must be individualized.”

To Prof. Snyder, the overarching issues are ones of money and attitude toward health.

The biggest barrier is ‘who pays?’ Our system right now is not incentivised to keep people healthy but rather treat them once they get sick.”

Prof. Michael P. Snyder

Advances in precision medicine have been closely linked to new technologies, and they are clearly changing the way that we diagnose and treat cancer, as well as our views on prevention as a method of treating long-term conditions such as diabetes.

Whether precision medicine will permeate all areas of healthcare and benefit patients from all walks of life, however, remains to be seen.

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