Circulating Tumor Cells: How Far Have We Come with Mining These Seeds of Metastasis?

Simple Summary Circulating tumor cells are cancer cells that detach from the primary tumor and enter the bloodstream. These cancer cells in the blood stream eventually result in secondary tumor growth referred to as metastasis. Research on circulating tumor cells is crucial because they can provide valuable insights into cancer progression and treatment response that enhances the patient outcomes. Findings from circulating-tumor-cell-based research can also shed light on cancer metastasis, drug resistance, and tumor evolution, ultimately benefiting the research community by advancing our understanding of cancer biology and guiding the development of innovative treatments. In this review, we have attempted to consolidate the milestones in CTC-based research and their utility in understanding the biology of cancer from origin to progression.Abstract Circulating tumor cells (CTCs) are cancer cells that slough off from the tumor and circulate in the peripheral blood and lymphatic system as micro metastases that eventually results in macro metastases. Through a simple blood draw, sensitive CTC detection from clinical samples has proven to be a useful tool for determining the prognosis of cancer. Recent technological developments now make it possible to detect CTCs reliably and repeatedly from a simple and straightforward blood test. Multicenter trials to assess the clinical value of CTCs have demonstrated the prognostic value of these cancer cells. Studies on CTCs have filled huge knowledge gap in understanding the process of metastasis since their identification in the late 19th century. However, these rare cancer cells have not been regularly used to tailor precision medicine and or identify novel druggable targets. In this review, we have attempted to summarize the milestones of CTC-based research from the time of identification to molecular characterization. Additionally, the need for a paradigm shift in dissecting these seeds of metastasis and the possible future avenues to improve CTC-based discoveries are also discussed.