NOVEMBER 2023LIFE SCIENCES REVIEW8ne of the most difficult aspects of oncology is the troublesome nature of tumor cells. They are hard to get rid of and can reappear at any time. To make matters worse, their lingering presence after a patient has finished treatment can drastically worsen that patient's prognosis. In addition to cancer relapse, tumor cells can become resistant to treatment and continue to thrive, leading to disease progression. The impact that surviving tumor cells, or minimal residual disease (MRD), have on patient prognosis makes the ability to detect their continued presence a crucial part of oncology research and therapy.To better identify the presence of tumor cells, oncologists are turning to next-generation sequencing (NGS). By sequencing the cell-free DNA (cfDNA) in a patient's bloodstream, oncologists can detect cancer mutations in DNA shed from cancer cells. The presence of these mutations in cfDNA indicates that tumor cells are present in the patient's body--and there is a growing body of evidence that cfDNA can be used to find lower levels of MRD than other currently available methods.Research into the detection of MRD is useful in several different contexts, from potential monitoring of disease progression to opportunities for tracking response to treatment. After a tumor is resected and the patient has undergone treatment, detecting MRD gives clinicians feedback on the effectiveness of the treatment and allows them to tailor care based on the patient's response. If tumor cells are still detected after treatment, this could suggest that the tumor might be resistant to treatment, thereby signaling the need for clinicians to reevaluate and decide if the patient would benefit from other options. If MRD is not detected, then clinicians can ease off harsh treatments and focus on keeping cancer in remission. After patients have been in remission, MRD detection can be used as a way to track if tumor cells are reemerging and quickly catch a relapse.Approaches to Detecting MRD There are two different ways that NGS is currently being used to detect MRD, depending on the information available to clinicians. When clinicians do not know which specific mutations are found in a tumor, they can sequence the cfDNA using a panel of universal cancer markers to detect the presence of MRD in a tumor-naïve approach. When clinicians have sequenced a tumor and know the mutations that it contains, they are able to take a tumor-informed approach and select a panel of markers that are specific for the mutations related to that patient's unique cancer cells. By using a panel that is designed to be personalized for that patient, they are able to optimize the sequencing to detect tumor cells at lower levels. Using panels to target only the genes that are relevant to a patient's tumor allows for those genes to be sequenced IN MY OPINIONBy Steven Henck, Ph.D., Vice President of R&D, Integrated DNA TechnologiesIMPROVING MINIMAL RESIDUAL DISEASE DETECTION USING NGSSteven Henck, Ph.D., is Vice President of R&D at Integrated DNA Technologies, a global genomics solutions provider helping to accelerate scientific breakthroughs. IDT has developed proprietary technologies for genomics applications such as next-generation sequencing, CRISPR genome editing, synthetic biology, digital PCR, and RNA interference. Visit www.idtdna.com for more information.o
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