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Personalized assay surpasses limits for detecting tumor DNA in breast cancer patients

August 07, 2019

Scientists have developed a personalized platform tailored to patients' specific cancer mutations named TARDIS, which was able to accurately detect circulating tumor DNA (ctDNA) and signs of residual disease in 33 women with breast cancer. Their technology demonstrated a hundredfold improvement in sensitivity compared to previous approaches. Although more testing is needed, the assay could one day be used to help monitor how patients respond to chemotherapy and to identify recurrences of tumors earlier on. In recent years, researchers have developed an array of techniques to detect or monitor cancers by examining ctDNA - DNA shed from the tumor site that circulates in the blood. However, ctDNA is often present in much lower amounts compared to circulating DNA from non-tumor cells, making it difficult to detect, especially in patients who have already received chemotherapy. This obstacle has impeded the creation of a platform sensitive enough to detect signs of recurring disease - a chief concern in many cancer patients. To solve this issue, Bradon McDonald and colleagues created TARDIS, a sequencing platform that analyzes patient-specific mutations from limited sample sizes. Their assay analyzes an amount of DNA equivalent to a single tube of blood and can simultaneously study eight to 16 known mutations. TARDIS successfully detected ctDNA in plasma samples from 33 patients with breast cancer before they started treatment, and revealed the patients had lower concentrations of ctDNA after treatment was completed. Furthermore, patients who responded the best to chemotherapy displayed a 96% decrease in ctDNA abundance, while patients with residual disease showed a 77% decrease - indicating the platform could guide the personalized management of patients at risk of cancer recurrence. In a related video, the researchers say that their findings must be validated in larger trials before TARDIS can be employed in the clinic. Next steps also include scaling up the platform for use in hundreds of patients.
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American Association for the Advancement of Science

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