Cancer metastasis chemoprevention prevents circulating tumour cells from germination

Abstract

The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law. The cancer crusade costs trillions with disappointing returns, teasing the possibility of a new breakthrough. Cure for cancer post-metastases still seems tantalisingly out of reach. Once metastasized, cancer-related death is extremely difficult, if not impossible, to be reversed. Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells (CTCs) from initiating metastases safely and effectively, and is disparate from the traditional cancer chemotherapy and cancer chemoprevention. Deep learning of the biology of CTCs and their disseminating organotropism, complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche (the first and the most important part in cancer metastatic cascade) can be pharmaceutically interrupted, the lethal metastatic cascade could be prevented from getting initiated. We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination, provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites. The adhesion/inhibition ratio (AIR) is defined for selecting the best cancer metastasis chemopreventive candidates. The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.

Isolation, Detection and Analysis of Circulating Tumour Cells: A Nanotechnological Bioscope

“…Likewise, CTCs also gained substantial hype as an important marker to understand the pathology as well as the efficacy of drugs against diseases. The pharmaceutical relevance of CTCs has been highlighted with recent research showcasing the role of different factors related to CTCs to understand their adhesions at the secondary metastatic sites [ 213 ]. Organoid culture platforms generated from CTCs have been used to understand the pharmacotypic signatures related to tumors and use them as a tool for personalized therapeutics domains [ 214 ].…”

Targeting of endothelial cells in brain tumours

“…Based on this principle, a novel chemoprevention paradigm for cancer metastasis has recently been proposed. 17 It differs from conventional strategies in that it emphasises the use of drugs to block the vascular adhesion of CTCs, thereby preventing the initiation of the lethal metastatic cascade.…”

“…As vascular adhesion is the first step in initiating metastasis in distant target organs, the leading cause of death in many cases of primary malignancy, its inhibition is a good strategy. Based on this principle, a novel chemoprevention paradigm for cancer metastasis has recently been proposed 17 . It differs from conventional strategies in that it emphasises the use of drugs to block the vascular adhesion of CTCs, thereby preventing the initiation of the lethal metastatic cascade.…”

Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells

“…Recent studies have shown that tumor-derived exosomes are involved in the formation of pre-metastatic niches (PMNs), which promote a favorable environment for the arrival and survival of metastatic cells at secondary sites [ 9 – 12 ]. It is crucial to PDAC’s metastasis that the PMNs shield the circulating tumor cells (CTCs) from apoptosis when they reach the metastatic location [ 13 ]. Exosomes released by cancer cells facilitate the development of PMNs by facilitating angiogenesis, stromal cell remodeling, extracellular matrix (ECM) remodeling, and oncogenic reprogramming [ 14 – 16 ].…”