Few would argue with the basic premise that early cancer detection is a good idea—it is generally the best prognostic indicator. Whether circulating tumor DNA (ctDNA) analysis, a potentially powerful but still emerging technology, is sufficient for that task is an open question for now—but one that Menlo Park, California–based Grail will be able to interrogate from multiple angles. Its ambitions extend beyond that goal, however. It aims eventually to lower the cancer burden by fostering new treatment paradigms that offer substantial improvements over current standards of care. “Otherwise you don't have utility, you just have detection,” says Mark Lee, Grail's head of clinical development and medical affairs.
That circulating DNA from cancer cells is present in blood has been recognized for decades, but the recent emergence of ultra-sensitive DNA sequencing methods has transformed its status from biological curiosity to invaluable analyte (J. Clin. Med. 6, E3, 2017). “From a technology standpoint, it's early days,” says Alex Aravanis, head of R&D at Grail. ctDNA-based testing is already used to guide therapy selection and to monitor treatment responses in patients with advanced cancer (Nat. Biotechnol. 34, 1090–1094, 2016). But early detection in otherwise asymptomatic individuals requires far greater levels of sensitivity, as the levels of ctDNA in circulation correlate with tumor burden. “The field has some anecdotal data—it's starting to become more than that,” he says. Grail expects to generate data for internal company use this year but will keep the CCGA study open until 2022 in order to follow participants' outcomes. It is by no means clear at this point, however, that ctDNA analysis will work for all cancers—levels of detectable ctDNA vary considerably across different indications (Sci. Transl. Med. 6, 224ra24, 2014).
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