It’s been more than 20 years since treatment for patients with leukemia led the way in the development of testing for minimal residual disease, also referred
to as measurable residual disease (MRD). It was pretty clear then that the key to detecting very small amounts of tumor revolved around the tumor’s DNA.
That is because DNA is made of two chains of complementary base pairs, and these can be multiplied and expanded either naturally (when cells divide) or artificially in a test tube using a process called polymerase chain reaction that uses some of the enzymes that are required in nature. If one or more mutations of the tumor are known, these assays for tumor-specific RNA or DNA are ultrasensitive.
MRD testing began among patients with chronic myeloid leukemia, a disease that lends itself to gauging MRD because it is driven by a specific genetic mutation, the BCR-ABL fusion, which is part of the Philadelphia chromosome that can be viewed under a microscope. It became very useful when newer drugs became available that target the abnormal growth-promoting enzyme (kinase) encoded by this mutation. As our knowledge has grown regarding mutations in other hematological cancers that are being targeted by a growing array of drugs, MRD assays can detect not only relapse at its earliest stage but also what new mutations are evolving that lead to resistance and can be addressed by switching to the appropriate new drug.
In this special issue of CURE dedicated to issues facing patients with leukemia and lymphoma, we take a look at the history of MRD testing, talk with experts about its benefits for patients during their cancer journey and discuss how this technique may benefit more patients in the future.
“[MRD testing is] really the future for guiding the very best therapies,” one doctor told CURE. “Over and over again, we’ve seen examples of how MRD is the best predictor for outcome and (how) it can help us know when to increase or decrease or change therapies.”
In the future, more and more diseases will be managed in a more timely, precise manner with these technologies.
DEBU TRIPATHY, M.D.
Professor of Medicine
Chair, Department of Breast Medical Oncology The University of Texas MD Anderson Cancer Center
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