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Preprint WatchMildJuly 28th, 2026

Circulating colorectal tumor cells remodel their surfaceome to increase their viability and metastatic potential in the bloodstream

Cabaud, O.; Aulas, A.; Lopresti, A. M.; Acquaviva, C.; Finetti, P.; Dessaux, C.; Ganier, L.; Da-Costa, Q.; Germier, C.; Mescam, L.; Elkaoutari, A.; Audebert, S.; Camoin, L.; de Rauglaudre, B.; Boudin, L.; Denicolai, E.; Lumet, G.; Cohendet, A.; Picard, M.; Birnbaum, D.; Gouarne, C.; Chanez, B.; De Chaisemartin, C.; Lelong, B.; Marchetto, S.; Goncalves, A.; Bertucci, F.; Borg, J.-P.; Mamessier, E.

PTK7 is highly expressed in primary colorectal tumours and metastatic lesions but is absent from most circulating tumour cells, undergoing a reversible tumour-on, circulating-cell-off, metastasis-on switch.

Mild contradiction

1 prior failure

One documented clinical failure (Phase 1 or 2) overlaps with the claimed mechanism.

The preprint reports that PTK7 is highly expressed in primary colorectal tumours and metastatic lesions yet absent from most circulating tumour cells, describing a reversible expression switch across the metastatic cascade. That observation speaks directly to pro1107-ptk7-solid-tumors-phase1-2-benefit-risk-discontinuation, a PTK7-directed antibody drug conjugate recorded in Claidex as a translational mismatch. An antigen that turns off in the disseminating population is a difficult target for a payload-delivery strategy aimed at preventing metastasis, and it offers a candidate explanation for a benefit-risk profile that did not support continuation. The flag is mild because a single prior failure carries limited weight, but the expression-switch claim is testable in archived trial samples.

Abstract excerpt

Circulating tumor cells (CTCs) are the potential seeds of distant metastases; however, little is known about how they survive in the bloodstream. Using a large cohort of colorectal cancer (CRC) patients, we found that the pseudokinase receptor PTK7 is highly expressed in primary tumors and metastatic lesions. Consistent with previous reports, high PTK7 expression is associated with reduced disease-free survival and increased metastatic dissemination. Surprisingly, PTK7 is absent from most CTCs and undergoes a cell-autonomous ONtumor/OFFCTC/ONmetastasis switch that can be recapitulated in a xenografted mouse model, in in vitro systems, and a fluidic platform. PTK7-negative cancer cells exhibit increased expression of YAP1-driven genes, senescence-like features, and enhanced resistance to hemodynamic stress following loss of cell-cell and cell-matrix adhesion. This adaptive phenotype depends on metalloproteases, notably ADAM17, whose cleavage activity remodels the CTCs surfaceome. Functionally, the PTK7 OFFCTC state confers enhanced metastatic potential in vivo, and can be pharmacologically suppressed using metalloprotease inhibitors. Collectively, our findings identify a reversible, cell-autonomous, protease-driven surfaceome remodeling program that enables metastatic adaptation during hematogenous dissemination.

Matching Claidex post-mortems

1 of 1 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.