Gauging the Impact of Cancer Treatment Modalities on Circulating Tumor Cells (CTCs)

Abstract

The metastatic cascade consists of multiple complex steps, but the belief that it is a linear process is diminishing. In order to metastasize, cells must enter the blood vessels or body cavities (depending on the cancer type) via active or passive mechanisms. Once in the bloodstream and/or lymphatics, these cancer cells are now termed circulating tumor cells (CTCs). CTC numbers as well as CTC clusters have been used as a prognostic marker with higher numbers of CTCs and/or CTC clusters correlating with an unfavorable prognosis. However, we have very limited knowledge about CTC biology, including which of these cells are ultimately responsible for overt metastatic growth, but due to the fact that higher numbers of CTCs correlate with a worse prognosis; it would seem appropriate to either limit CTCs and/or their dissemination. Here, we will discuss the different cancer treatments which may inadvertently promote the mobilization of CTCs and potential CTC therapies to decrease metastasis.

Portal Venous Circulating Tumor Cells Undergoing Epithelial-Mesenchymal Transition Exhibit Distinct Clinical Significance in Pancreatic Ductal Adenocarcinoma

“…EMT and its different intermediate status have recently been noticed as crucial drivers of tumor progression and metastasis (16,24,25). In light of recent research demonstrated that the CTC count could be used as a prognostic biomarker, and a higher CTCs count may predict an unfavourable prognosis in malignant patients (26)(27)(28)(29)(30). In this research, we used the Canpatrol ™ CTC filtration platform to detect CTCs in different EMT statuses intend to explore their prognostic assessment value.…”

Circulating tumour cell and cell-free DNA kinetics during radiotherapy in patients with intact head and neck squamous cell carcinoma

“…The notion that local cancer therapy, such as surgery and radiotherapy, can potentially mobilize tumour cells into the systemic circulation and potentially influence the risk of development of distant metastatic disease, is not novel. Several surgical studies have reported an increase in CTC counts during and/or after oncological surgery in patients [18-23]. With regards to radiotherapy, although not demonstrated in human studies until more recently, Kaplan and Murphy [24], in 1949, showed that lung metastases were more common in tumour-bearing mice that received radiotherapy than those were not irradiated.…”

The matrix-dependent 3D spheroid model of the migration of non-small cell lung cancer: a step towards a rapid automated screening

“…Notably, in NSCLC there was no association between CTCs and long-term survival of the patients observed (Barr et al, 2020). While mechanisms of "classical" metastasis cascade are well-studied (Dianat-Moghadam et al, 2020), there is a gap of knowledge of the mechanisms of post-surgical invasion of the secondary tissue by the CTCs, as current knowledge about CTCs biology is very limited (Mathias et al, 2020). The mechanisms of the postsurgical CTCs wound implantation and local migration into the secondary tissue (often not involving entry into the bloodstream) potentially leading to the metastasis within the surgical scars are undoubtedly different compared to "classical" metastasis, because of the alteration in the composition and structure of the surgically damaged target tissue (for example, disrupted basal membrane), the influence of the post-surgical inflammatory milieu, as well as specific phenotypic characteristics of the post-surgical CTCs clusters (for example, difference in the level of expression of EMT markers by CTCs, stromal cell composition within the CTCs, and others).…”