Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers

Free-flowing cancer cells have been mapped with unprecedented accuracy in the bloodstream of patients with prostate, breast and pancreatic cancer, using a brand new approach, in an attempt to assess and control the disease as it spreads in real time through the body, and solve the problem of predicting response and resistance to therapies.

The field of circulating tumor cell (CTC) research has evolved rapidly in response to a significant unmet medical need for longitudinal disease monitoring in patients with epithelial cancers (carcinomas). Predicting and monitoring therapy response and disease progression are particularly important due to changes in the therapy-responsiveness of disease over the course of a patient’s cancer. In liquid tumors such as leukemias, the malignant cells can be easily sampled from the bloodstream at many points during the disease, and appropriate therapy adjustments applied. However, solid tumors such as carcinomas are generally sampled only at the time of initial diagnosis, as tissue biopsies are invasive procedures with known risks. Occasionally, a repeat tumor sampling is collected at the time when distant metastasis first becomes apparent, to confirm that distant lesions in fact represent metastases from the patient’s known primary tumor. Thus, in our understanding of cancer behavior, while progress has been made in understanding the solid tissue forms of primary and metastatic carcinomas in their respective microenvironments, a substantial gap exists in understanding carcinoma behavior during the fluid phase, wherein it occupies and spreads via the bloodstream. For cancers that occur predominantly as solids, the elusive and scant circulating component contains within it the cells giving rise to future distant metastases, and as such, represents a compelling target for investigation.

Research to fully characterize the clinical significance of this fluid phase of solid tumors has been hindered by the lack of easily accessible and reliable experimental tools for the identification of CTCs. The unknown character and low frequency of CTCs in the blood, combined with the difficulty of distinguishing between cancerous versus normal epithelial cells, have significantly impeded research into how the fluid phase might be clinically important. The ideal fluid phase biopsy would find significant numbers of CTCs in most epithelial cancer patients, and would preserve and present CTCs to a diagnostic pathologist and/or researcher in a format that enables not only enumeration but further molecular, morphologic and/or phenotypic analysis. In addition, it should preserve all other CTC-like cell populations within the sample for further analysis

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