Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Abstract

Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers

“…Tumors can suppress immune editing or cause a pro-inflammatory condition due to the use of cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). They can also stimulate pericytes and endothelial cells to promote angiogenesis [14] . They can influence activities of intrinsic signaling pathways of the neighboring cells to better detach and invade in the form of circulating tumor cells [15] .…”

Revealing Molecular Mechanisms of Early-Onset Tongue Cancer by Spatial Transcriptomics

“…The genes specific to the last cluster of four early-onset TSCC cases were analyzed for association with overall survival using the Human Protein Atlas Kaplan-Meier plotter tool [12]. The focus on the last cluster was related to the suggestion that during the transition of tumor cells from a lower to higher malignant state, some genes are silenced, while others become active, thus predicting aggressiveness and early recurrence of cancer [13, 14]. High expression of the FSCN1, FADS3, BRI3 , and CYB5B genes was found to be associated with worse overall survival of head and neck cancer patients (Supplementary Figure S1).…”

Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics

“…The genes speci c to the last cluster of four early-onset TSCC cases were analyzed for association with overall survival using the Human Protein Atlas Kaplan-Meier plotter tool 13 . The focus on the last cluster was related to the suggestion that during the transition of tumor cells from a lower to higher malignant state, some genes are silenced, while others become active, thus predicting aggressiveness and early recurrence of cancer 14,15 . High expression of the FSCN1, FADS3, BRI3, and CYB5B genes was found to be associated with worse overall survival of head and neck cancer patients (Supplementary Fig.…”