Rapid translation of circulating tumor cell biomarkers into clinical practice: technology development, clinical needs and regulatory requirements.

The great hope in circulating tumor cell (CTC) research lies in the use of these rare cells as an accessible "fluid biopsy" that would permit frequent, minimally invasive sampling of tumor cells for similar molecular assays that are performed on traditional biopsies. Given the rarity of CTCs in peripheral circulation, microscale methods show great promise and superiority to capture and analyze these cells from patients with solid tumors. Novel technologies that produce validated CTC biomarkers may finally provide medical oncologists the tools needed to provide precise, personalized medical care for patients with advanced cancer. However, few CTC technologies demonstrate both experimental and clinical evidence of an accurate, reliable and reproducible assay that also meets the regulatory requirements to enter routine clinical practice. Many opportunities exist to incorporate clinical needs and regulatory benchmarks into technology development to more quickly garner FDA approval to direct decisions on patient care. This review will address: 1) device development tailored to address predictive, prognostic and/or therapeutic needs across the multitude of malignancies and disease stages; 2) validation benchmarks for clinical assay development; 3) early establishment of standard operating procedures for sample acquisition and analysis; 4) demonstration of clinical utility; 5) clinical qualification of a novel biomarker; and 6) integration of a newly validated and qualified technology into routine clinical practice. Early understanding and incorporation of these regulatory requirements into assay development can simplify and speed the integration of these novel technologies into patient care. Meeting these benchmarks will lead to the true personalization of cancer therapies, directing initial and subsequent treatments for each individual based on initial tumor characteristics while monitoring for emerging mechanisms of resistance in these continually evolving tumors.