BRCA Journal

journal entry

Feb 28


How Can Our Data Keep Us Healthy?

"How do you envision a patient’s visit to a doctor in the future?" was my final question. I was interviewing Evan Goldberg, founder of the BRCA Foundation and a Silicon-Valley-big-data-guy, about the role of big data in cancer research and care. Doing phone interviews is something I never felt comfortable with. I was nervous but prepared, or so I thought. My questions were thoughtfully answered and the voice recorder application on my phone was turned on. Unfortunately, I cannot tell you exactly how Evan answered the question because the app did not record his end of the conversation! Battling my embarrassment and disappointment, I instantly wrote down what I remembered to be his answers. The document ended up being the blueprint for this series exploring the impact and implications of big data and precision medicine. His answers armed me with information that helped frame the ultimate question, "How will big data transform our visit to the doctor?"

In the first post of the series, How "All of Us" Can Contribute to Precision Medicine, I addressed the Precision Medicine Initiative (PMI) and its projected active cohort of one million participants named "All of Us". In short, the PMI aims to collect "health data" from these volunteers and securely provide them to researchers and clinicians so they may be analyzed. Studying the different parameters of health, from people’s genomes to their lifestyle, will highlight the molecular makeup and origin of disease and elucidate how those differ between patients. Down the line, this knowledge will help develop tools, tests, and drugs to prevent, diagnose, and treat diseases more precisely and efficiently. The obvious short-term focus of the PMI is cancer. A devastatingly common occurrence, cancer is one of the most diverse groups of diseases that affect people differently due to their genetics and/or environment. Today, individuals have limited amount of viable options to prevent, diagnose, or treat cancer. Even successful treatment plans have devastating side effects on the patient’s mental and physical well-being.

Improve the User Manual

Using data from "All of Us," the PMI wants to develop new options and personalize them through various avenues. Some options are actually already offered but need a clearer and more precise "user manual." Tumors are heterogeneous and different individuals respond differently to available cancer drugs. Currently, doctors resort to trial and error when deciding on treatment plans for a large number of cases. This means some patients have to endure multiple therapy options before they respond successfully. Some are sent home because doctors cannot predict what treatment would be safe and effective for their late-stage cancer. In fact, we don’t know why some tumors are resistant or sensitive to certain treatments and not others, and why some develop resistance to those treatments over time. The most common issue is not that there is no cure for some tumors (though that remains an issue); it’s that we do not know what cure to give which patient at what time. The low hanging fruit for the PMI, then, is to use big data to match which available and approved treatments work individually or together on which specific molecular tumor profiles. Little is actually known about how drug combinations can work together to maximize their potential. This approach to therapy is gaining momentum in the cancer field, both in pharma and academia. Last July, Merck and AstraZeneca, two big pharmaceutical companies, announced their collaboration to test the combination of targeted PARP and MEK inhibitors with PD-L1/PD-1 immunotherapies. The hope is to attack the tumor on two different fronts so it has no place left to hide and survive. Collectively, the resulting treatment plans might not all be targeted per se, but will be more informed and deliberate. This will save more lives and make cancer care less wasteful and more affordable.

Generate Targeted Therapies

The ultimate goal, of course, is to have targeted therapies based on the molecular tumor profiles established by the PMI big data studies. At the moment, most chemotherapies affect both normal cells and cancer cells. They indiscriminately target all fast-growing cells, which causes the common side effects of hair loss and nausea. Targeted therapies, on the other hand, primarily target cancer cells. Since many different pathways can be altered for normal cells to turn cancerous, therapies should be tailored to the resulting cancer at hand. We are still in the process of understanding the players involved in these molecular pathways but data from "All of Us" can uncover novel ones to target. This approach, albeit on a bigger scale, echoes earlier successes in precision medicine. Knowing the molecular and genetic background of certain cancer cells is what led scientists to develop or repurpose drugs that home in on the specific molecular changes those cells underwent. PARP inhibitors are the perfect example of such drugs; in their case, they work effectively on BRCA mutated cancer cells. Discovering and understanding the other pathways and players that change in BRCA positive cancers can lead to even more targeted and effective therapies. We have to keep in mind, though, that developing more targeted therapies does not have to be a complicated and expensive approach. The power in investigating the molecular changes in cancers is not only in understanding how they differ but how they are alike. Finding commonalities will aid in the discovery of drugs or drug combinations that are specific enough for a number of different cancer profiles and not just one.

Develop Methods to Assess Risks and Detect Tumors

Therapies are important but they are only half the battle. Early detection is vital because the earlier a tumor is identified, the better the long-term survival. We still, however, lack accurate methods to detect cancers early. Both ovarian and prostate cancers, for instance, do not have a known and reliable early biomarkers that can detect or diagnose malignant tumors. "All of Us" can help find and utilize these biomarkers and develop reliable tests. Evaluating when and to whom to give those tests is also important and has major implications for BRCA mutation carriers. Right now, doctors have few recommendations for BRCA mutation carriers, one of which is prophylactic surgery. Some carriers, however, develop breast cancer and some develop ovarian cancer, while 40% of the others do not develop cancer at all. Studying the population at large through "All of Us" can reveal other risk factors and/or biomarkers that may help assess the cancer risk for BRCA mutation carriers beyond BRCA genetic testing. This will help carriers be more informed about, and secure in, their medical decisions and reduce the number of unnecessary surgeries. On the other end, we also lack sufficient methods for monitoring tumor responses to treatment and tumor recurrence after treatment. Some cancers cells, after developing resistance to a certain therapy, will start growing again once the patient has recovered. Knowing how cancer cells are responding to a drug and catching them before they hide and develop resistance is key to long-term survival and health. "All of Us" will help form the basis for novel and compressive tumor monitoring techniques and devices.

Active Participants in Our Health

Besides all the promising clinical and health care revolutions to which "All of Us" will contribute, its potential impact on the public’s engagement in their own healthcare is perhaps the most culturally transformative. Being part of "All of Us" will make us active participants in not only identifying tools to help cure people but in learning and understanding our own bodies. We can access and use our data ourselves to better understand our genetics and the specific implications of our diets and lifestyles. Consequently, we will no longer be passive patients but engaged individuals who monitor and take a more active role in our health. Learning about our genetic variants will change how we think about our blood pressure and our risk for developing diabetes or even cancer. It will also enable us to easily take part in clinical trials that help us and our communities improve health outcomes overall. For my part, I cannot wait to get off the waiting list and start donating my data to "All of Us". The decision to get up-close and personal with the PMI was not as easy as I expected though. I worried, as many would, about the security and privacy of my health data. I will explore these concerns and what changed my mind in my next and final blog post of this series.

Author Bio

Rabab is a postdoctoral scholar at the University of California, San Francisco, working on how newborn nerve cells travel and mature in the developing brain. When not at the bench, she is an avid STEM advocate and a science communicator who contributed to science blogs throughout her graduate studies at the Albert Einstein College of Medicine. In her free time, she likes to read articles on Flipboard and dance the Lindy Hop.