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Getting into the bloodstream kills almost every cell that tries: cells are ripped from their neighbours, battered by flow, and hunted by NK cells. Fewer than one in a thousand survive. The ones that do travel in clusters, wear a cloak of platelets, or ride with neutrophils. Liquid biopsies catch what is left.
Intravasation happens at 'TMEM doorways' (a tumour cell, a perivascular TIE2+ macrophage and an endothelial cell in direct contact) where macrophage-derived VEGF-A transiently opens the vessel; leaky angiogenic vessels and lymphatics (VEGF-C) also admit cells. In the blood, detachment triggers anoikis (integrin loss → BIM/BMF → apoptosis), which metastatic cells resist via TrkB, PI3K, and mesenchymal states; shear stress and oxidative stress (antioxidants paradoxically aid metastasis) kill most; NK cells clear the rest. Survivors use platelet cloaking (P-selectin, tissue-factor-thrombin, platelet TGF-β shielding from NK and inducing EMT), neutrophil escorts and NETs, and travel as clusters held by plakoglobin and CD44, which are up to 50-fold more metastatic than singles and carry hypomethylated stemness genes. CTCs (EpCAM-based CellSearch; ≥5 per 7.5 mL prognostic in breast, prostate, colorectal) and ctDNA are the clinical windows; fragmentomics and methylation extend detection. Aspirin and anticoagulants reduce metastasis in models via the platelet arm; Na+/K+-ATPase inhibitors dissolve clusters preclinically.
Leaving a fortress through the drains and swimming a river in flood while archers (NK cells) fire from the bank. Survivors go in rafts (clusters), under wet blankets (platelets), and with a friendly escort (neutrophils).
It turned a single-centre observation into a prospectively validated one and concluded that AR-V7-positive men should be offered alternatives to abiraterone and enzalutamide. It also quantified the honest limit: two assays for the same analyte disagree on nearly one sample in five.
It is the clearest evidence in prostate cancer that a blood biomarker can point to one treatment class over another, and the reason AR-V7 is discussed in guidelines despite being in no label.
Two pathway pages and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
The first predictive resistance biomarker in prostate cancer, and a mechanism rather than a correlation: a receptor with no ligand-binding domain cannot be blocked by a drug that binds the ligand-binding domain. It is also the origin of the case for androgen receptor degraders, which destroy the protein rather than blocking a site the protein no longer has.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares Seed and soil hypothesis of metastasis (Paget), The pre-metastatic niche, The metastatic cascade, Metastasis is understood least and studied last and the tags mechanism, mechanics-atlas.
Shares Continuous and near-continuous ctDNA monitoring, Signatera, Dormant cells and minimal residual disease, Minimal / molecular residual disease (MRD) and the tags mechanism, mechanics-atlas.
Shares Hallmark: activating invasion and metastasis, The metastatic cascade, Epithelial-mesenchymal transition & drug efflux and the tags mechanism, mechanics-atlas.
Shares CSF1R, The angiogenic switch & tumour vessels, VEGF / VEGFR and the tags mechanism, mechanics-atlas.
Shares CSF1R, NK-cell recognition: missing self & stress ligands and the tags mechanism, mechanics-atlas.
Shares PROPHECY: prospective multicentre validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer, AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer, PIK3CA / PI3K-alpha, Liquid biopsy (ctDNA) and the tags mechanism, mechanics-atlas.
Shares CSF1R, PIK3CA / PI3K-alpha, VEGF / VEGFR and the tags mechanism, mechanics-atlas.
Shares CSF1R, VEGF / VEGFR and the tags mechanism, mechanics-atlas.