Q&A: Getting Personal from Lab to Clinic
The way we diagnose and treat cancer is fundamentally changing. Today it’s clear that a one-size-fits-all approach to treatment may not fit at all. Medicine has become increasingly personalized, meaning finding the right treatment for each individual patient. Many factors are leading to this shift in practice, and we’re now at an inflection point in the evolution of personalized medicine that is changing the future of oncology.
To explore this evolution, we sat down with a lab researcher and a clinician — two of the integral roles in personalizing medicine. Researchers like Garret Hampton, Ph.D., study the biology of cancer to develop biomarkers and diagnostic tests that pinpoint the genetics underlying cancer. Clinicians like Josina Reddy, M.D., Ph.D., translate this biologic understanding of cancer into the development of new medicines.
What’s the driving force behind the evolution of personalized medicine?
Garret Hampton: The key driver for personalized medicine is the realization that most common human diseases, including most cancers, are heterogeneous, resulting from different molecular drivers that fuel the disease. For example, we now know that two women with breast cancer whose disease looks similar under the microscope can have very different diseases at the molecular level, requiring different treatments. The advancements in genome sequencing and the explosion in the amount of data about disease heterogeneity have become the foundation of personalized medicine.
The more information we have, the better we can understand the role of different mutations in disease, develop biomarkers and identify the right medicines for the right patient. If we can bring all of this together we can identify the biological basis of disease in each individual patient so we can treat disease much more precisely.
How has a deeper understanding of cancer biology translated to new medicines?
Josina Reddy: At the end of the day, understanding the biology of each person’s cancer doesn’t directly benefit that person unless you can offer an effective and safe treatment that addresses that biology. All these new data and knowledge are helping us to use existing treatments better, to develop new medicines and to study their potential uses in combination with each other. It’s even leading to entirely new types of treatment, like cancer immunotherapies.
As we test new approaches, gather more data, and assess what works and why, it’s requiring significant innovation in how we study new medicines. New clinical trial designs, such as basket and umbrella trials, are designed from the ground up to personalize treatment by matching multiple types of cancers to a potential treatment based on the same underlying mutation, or by studying how multiple potential medicines work against one type of cancer that might have various underlying molecular drivers.
Basket studies enroll people with the same genetic mutation, regardless of its location in the body, and treat them with the same medicine or combination.
Umbrella studies test multiple medicines or combinations, each targeting a pathway in tumors of the same organ system.
These studies help us efficiently translate our hypotheses from the lab to real patients because they allow us to learn more about the disease and the potential of different treatment regimens when they are studied together. These approaches work especially well for rare forms of cancers where we often cannot enroll enough people in a traditionally designed study. These are just some of the approaches we’re already using to accelerate development of new cancer medicines.
What’s the most exciting way we are approaching personalized medicine in oncology?
Josina Reddy: Targeted therapies are the poster child of personalized medicine, because they’re designed to attack specific pathways driving tumor growth and are often paired with a biomarker to select the patients most likely to benefit. We’re starting to combine medicines with targets within these pathways and across multiple pathways, which can help delay or prevent the development of resistance. In the future, we’ll increasingly have the information we need to pick the right combination for each person with cancer.
An analogy is how treatment for HIV has evolved. First, there was one type of viral inhibitor available, then more kinds of inhibitors were developed, and now doctors give a cocktail of multiple kinds of inhibitors up front to fully suppress the virus and delay or hopefully prevent future resistance. We’re trying to do the same for cancer. This also presents the challenge of figuring out which combinations are most likely to work among the thousands of potential combinations, for many different patients according to their biomarker profiles. We are using clinical trial and regulatory innovation to move this field forward, because traditional methods aren’t well suited to evaluating these truly personalized therapeutic combinations.
Multiple Targeted Medicines
Endless combinations designed to treat many different types of cancer
You mentioned cancer immunotherapies. How are they personalized?
Josina Reddy: Immunotherapies are medicines that aim to activate our own immune systems to fight cancer, and we think eventually they’ll become just as personalized as targeted therapies. Immunotherapies may work differently in different people, and given the uniqueness of each person’s immune system, the biomarkers for immunotherapies will probably be more complex. Studying this complexity will help us determine which single immunotherapy, immunotherapy combination, or combination of immunotherapy with targeted medicines or other standard therapies, such as chemotherapy or radiation, will most effectively treat that unique tumor.
How have diagnostics helped evolve personalized medicine?
Garret Hampton: The availability of more sophisticated diagnostic tools in recent years is accelerating the transition to personalized medicine. It started with being able to identify a single genetic mutation in a tumor sample and treat that person with a targeted medicine. Now, new technologies that allow much more comprehensive and accurate detection of mutations are helping us measure things we couldn’t have ten years ago.
New tests are becoming available that interrogate all of the genetic alterations in a patient’s cancer to match a patient with an approved medicine, or a medicine in clinical development. Doctors will also be able to look at how similar patients with the same biomarkers fared with different treatment regimens.
What’s the most interesting recent technological advance in diagnostics? Where are we going in the future?
Garret Hampton: An emerging diagnostic technology is a test that can identify a cancer’s genetic alterations in the blood stream. It works because tumor cells and tumor DNA are sometimes shed into the blood stream, so they can be extracted and tested. The advantage is this allows people who are too unhealthy to undergo a biopsy or who lack sufficient biopsy material to be tested to guide their treatment. The test can also be repeated over and over, so we can monitor the effect of the therapy and identify when a cancer is recurring, unlike an invasive tissue biopsy that can only be done once or twice.
That being said, it’s a big step to move from testing people for single biomarkers to multiple biomarkers, or even panels of biomarkers, but as we work through each challenge incrementally it will add up to a huge shift in our ability to personalize treatment for cancer.
A Blood Test for Lung Cancer
What does the new age of personalized medicine mean for patients?
Josina Reddy: Right now, the amount of data and information can be overwhelming for doctors and for patients. We sometimes don’t know enough to separate the signal from the noise. It will take a lot of work to understand how to take advantage of everything we’re learning and how to implement that into effective treatment strategies. This means doctors and patients will continue to face a decision-making process full of complexity and uncertainty.
How far do you think we are from truly personalizing treatments?
Garret Hampton: For now, you can think of personalized medicine as science in motion. We’re working in the middle of a revolution, and it’s hard to see how much progress we have made. I’m an optimist, but it’s just going to take some time. I firmly believe we’ll get to the point in the next five to ten years where we’re truly tailoring treatment to gain the greatest treatment benefit. That’s the kind of work that we and many others are trying to do.
Josina Reddy: We’re in the midst of a continually evolving process. It’s a collective mission that we’re all in on; researchers, clinicians and people with cancer who need better treatments. Researchers and clinicians need to continue to sort through data, identify drivers of disease and develop new medicines. The people with cancer who so generously volunteer to participate in studies are at the center of these developments, because they enable the breakthroughs that come from clinical trials.
By working together, we’ll build a more comprehensive view of cancer biology and a better chance to make personalized medicine a reality for all people with cancer.
1Yoon HJ, et al. Radiology 2012
2Chouaid C, et al. Lung Cancer 2014
3Roche Internal Market Research, EU