Individual genome sequencing will become part of any treatment
Imagine trying to treat pneumonia with insulin. Pretty quickly, you’d decide that pneumonia is hard to treat or insulin isn’t much of a drug. Neither conclusion would be true, of course. Pneumonia is effectively treated with antibiotics. Biosynthetic insulin saves the lives of millions of diabetics daily.
The point, as my colleague Dr. Razelle Kurzrock often says, is that a drug’s effectiveness depends upon matching it to the right disease or target. This might seem obvious, but often it is not the case. New cancer drugs and therapies, for example, have long been developed in large, lengthy, expensive clinical trials where success is measured by improvements that last only a few weeks.
What happens to drugs and treatments that don’t have a widespread effect but do provide deep, perhaps profound, benefit to a few patients? Typically, they’re abandoned.
The overarching goal is to create therapeutics with the broadest, most-profitable bang for the buck, not necessarily therapeutics with the greatest efficacy. Drugs and treatments that help only a few patients are considered inefficient and cost-prohibitive. They are orphaned and often forgotten.
This hard reality of medical science is nowhere more apparent than in cancer, a villain that morphs into hundreds of henchmen. There are more than 200 types of cancer — from breast cancer to Waldenström’s macroglobulinemia. Each type presents its own challenges. A treatment that works in some patients won’t in others, even if they have the “same” cancer type.
As I’ve mentioned in previous columns, personalized cancer medicine is a fundamentally different approach to addressing this challenge. It fashions therapies and medicines based upon the precise, particular circumstances and needs of each patient. It’s one reason why individual genome sequencing will become, in the not-too-distant future, a routine part of any treatment. With a detailed clinical, social, genetic, genomic and environmental biography of each patient, doctors can more precisely tailor treatment to each patient. This is medicine matched down to the molecule.
Achieving this kind of precision requires serious basic research. Massive cancer genome sequencing efforts by government-funded consortia, such as The Cancer Genome Atlas and the International Cancer Genome Consortium, reveal a dauntingly complex landscape of DNA sequence changes in tumor cells.
It turns out that tumors from patients with the same cancer can look completely different at the genomic scale. Clinicians and researchers need to think differently about how to diagnose and treat cancer. They must think genomically. Our understanding of the human genome is still in its infancy, but early results indicate that personalizing drugs based on the list of DNA alterations in a tumor can be very successful.
Clinicians, basic scientists and bioinformatics researchers across the mesa are tackling this challenge together. They come from The Scripps Research Institute, the Salk Institute for Biological Studies, Sanford-Burnham Medical Research Institute, J. Craig Venter Institute, UC San Diego Moores Cancer Center and the San Diego Supercomputer Center, which houses some of the most advanced computing resources in the world.
Research resources at all of these institutions, such as cell sorters to isolate rare cancer stem cells and high-throughput machines to sequence tumor-cell DNA, are integral to this effort.
This work in cancer genome sequencing will be invaluable to us in building a robust, world-class system that matches each new cancer patient with the latest molecular technologies and therapeutics most likely to achieve the best, fastest results.
Quick intervention is critical. More than 90 percent of all cancer deaths are due to metastasis, the spreading of cancer from its original tumor site. The impetus is to find what works based upon individual patients, not upon broad cancer types. It is essential to design a protocol that makes every patient a clinical trial of one.
Dr. Kurzrock has developed just such a protocol, called PREDICT, or Profile-Related Evidence Determining Individualized Cancer Therapy. She is implementing such a protocol at Moores Cancer Center.
Before coming to San Diego, Dr. Kurzrock earned wide acclaim for developing one of the largest and best phase 1 clinical trials programs in the nation at the University of Texas M.D. Anderson Cancer Center. Hallmarks of that program were innovative clinical trials with new, targeted therapies, and matching patients with drugs based on their molecular profile. Now she is building on this effort in the new Center for Personalized Cancer Therapy, a major initiative of Moores Cancer Center.
This is complex work. It requires extraordinary resources ‒ human, scientific and technological. But as we proceed and progress, we will better learn what works and why. Each patient and every case will add to our armamentarium of knowledge and abilities.
That’s how you beat cancer: One patient at a time.
Note: You can hear Dr. Kurzrock talk about winning the war against cancer in the genomics era at a free public lecture 6-7:30 p.m. Dec. 4, at the Reuben H. Fleet Science Center in Balboa Park. To register for the event, presented by the Center for Ethics in Science & Technology and UC San Diego Extension, visit http://www.ethicscenter.net/Emperor-December2013.
—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 the La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman at firstname.lastname@example.org
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