In recent days and weeks, you’ve probably seen or heard reference to the All of Us Research Program, an effort to collect the genetic, biological, environmental, health and lifestyle data of at least 1 million volunteer participants living in the United States.
All of Us is unprecedented in both scope and aspiration; its grand goal to create a massively rich database researchers can mine for clues to new treatments and cures for almost everything that ails us. The $1.4 billion project is slated to run a decade, with findings and benefits to flow for many years beyond.
But one needn’t wait for All of Us to see the work and benefits of precision medicine — the idea that treatments can and should be tailored to the unique circumstances of each patient. Cancer scientists and doctors have been pushing and practicing the idea for several years, nowhere more so than at Moores Cancer Center at UC San Diego Health.
It makes sense. There are more than 200 cancers, with every cancer unique to each patient — its development, progression and treatment response influenced by the patient’s particular genetic makeup, health status, lifestyle, environment and other factors.
Historically, when scientists have explored the potential of new therapies, they have needed to conduct large, lengthy clinical trials involving hundreds, perhaps thousands, of participants. Yet the response rate to a tested “successful” drug or treatment might prove disconcertingly minute, generating a therapeutic benefit in only a relatively tiny percentage of participants.
Or perhaps more vexing, the benefit could prove transient or increase patient survival rates by just a few months, prompting many to question the use of such treatments at all (especially when treatment involves serious adverse effects or impinges upon quality of life).
Not surprisingly, it’s hard to recruit participants to trials when the chance of success can be small. Recruitment of qualified participants for clinical trials is among medical science’s most persistent problems.
But there is hope for a better future. Advances in genomic technologies and an increasingly detailed understanding of how genes and mutations drive different cancers (or hinder treatments or cures) are changing the game.
For example, the National Cancer Institute (NCI)-MATCH trial is currently recruiting hundreds of patients with multiple kinds of cancer, each assigned a treatment based genetic changes found in their tumors through genomic sequencing and other tests.
“This is one of the reasons why I’m so enthusiastic,” said NCI director Ned Sharpless, M.D. “I feel like we’re looking at the future. You write these big basket trials that can take all comers and allocate them to an arm of therapy. If you have enough arms of therapy and the drugs are good enough, then patients will really want to participate.”
A lot of them are San Diegans — or patients who come to Moores Cancer Center for their treatment. MCC researchers and physicians conduct roughly 300 clinical trials each year. Increasingly, they are next-generation trials, driven by the power of personalized cancer therapies, such as on-going PREDICT, co-led by Razelle Kurzrock, M.D., director of the Center for Personalized Cancer Therapy and Clinical Trials office, and Jason Sicklick, M.D., associate professor of surgery. PREDICT seeks to understand how well molecular testing can predict patients’ response to therapy. Another is DART, led by Kurzrock and Sandip Patel, M.D., assistant clinical professor, which is a national trial testing new immunotherapies on 80 rare cancer types.
The DART trial is open at 700 sites nationwide, but its purpose is quite narrow and highly refined.
“NCI-MATCH and DART are examples of novel clinical trial designs based on molecular characteristics or focused on rare tumors, neither approach which has been taken previously in widely available clinical trials,” Patel said. “Both are modular trials that adapt with the science and have the flexibility required to evolve with rapid evolution in therapeutic science. By creating trials that are for the patients, as opposed to patients being there for the trials, we potentially help more patients, which leads to more accrual, which can help more patients.”
Cancer is personal. So too should its remedy. In the next five years, says Ezra Cohen, M.D., associate director of translational science at MCC, all cancer patients are going to get some sort of next-generation sequencing of their genetic makeup. “This is not stoppable and will mean that centers will begin to do what Razelle and Sandip are already doing now.”
For the benefit of all of us.
— Scott M. Lippman, MD, is director of UC San Diego Moores Cancer Center. His column on medical advances from the front lines of cancer research and care appears in La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman by e-mail: firstname.lastname@example.org