Preprint Watch 2026-05-24: 1 Clinical Failures Flagged for EGFR | Claidex

Q: Why was this EGFR preprint flagged?

1 prior Claidex failure claim matched the target-disease mechanism. This bioRxiv preprint reports on EGFR biology in a setting adjacent to 1 indexed Claidex claim(s). The dominant mechanism described in the abstract is signaling pathway architecture, which does not directly replicate or contradict the failure modes documented in the matching post-mortems (bg-60366-egfr-cdac-nsclc-strategic-shutdown). The closest contact with the failure record is that any new EGFR-directed program should explicitly address the prior efficacy or strategic failures cataloged in those posts before opening a new Phase 2 design.

Claidex Preprint Watch

doi:10.64898/2026.03.20.712775

Preprint WatchMildMay 24th, 2026

Time-Resolved Phosphoproteomics-Guided BFS Beam Search Reveals Cell-Type-Specific EGFR Signaling Architectures and SHP2 Inhibitor-Induced Pathway Rewiring

Lee, H.; Lee, G.

Time-Resolved Phosphoproteomics-Guided BFS Beam Search Reveals Cell-Type-Specific EGFR Signaling Architectures and SHP2 Inhibitor-Induced Pathway Rewiring

Mild contradiction

1 prior failure

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

This bioRxiv preprint reports on EGFR biology in a setting adjacent to 1 indexed Claidex claim(s). The dominant mechanism described in the abstract is signaling pathway architecture, which does not directly replicate or contradict the failure modes documented in the matching post-mortems (bg-60366-egfr-cdac-nsclc-strategic-shutdown). The closest contact with the failure record is that any new EGFR-directed program should explicitly address the prior efficacy or strategic failures cataloged in those posts before opening a new Phase 2 design.

Abstract excerpt

Adaptive resistance to kinase- and phosphatase-targeted therapies is frequently driven by pharmacological rewiring of intracellular signaling networks, yet systematic computational methods for quantifying cross-condition pathway changes from phosphoproteomic data remain limited. We present an algorithmic framework for reconstructing cell-type-specific signaling pathways from time-resolved phosphoproteomic data using Breadth-First Search (BFS) combined with interaction-weight-guided Beam Search over the STRING protein-protein interaction database. The framework integrates the data-adaptive Median Absolute Deviation (MAD)-based binary-state assignment, BFS Beam Search traversal anchored to experimentally supported active nodes at zone boundaries and terminals (with STRING-inferred bridge proteins permitted as intermediate connectors), and a post-enumeration path cleaning pipeline that produces biologically interpretable, acyclic signaling routes (with edge-level validation against Human Protein Atlas-based cell-line expression data), with real-time access to the STRING REST API (v12.5), enabling network construction without local database installation. Benchmarked across five published phosphoproteomic datasets spanning three cell types (HeLa, MDA-MB-468, EGFR Flp-In HEK293T), the framework captures cell-type-specific EGFR signaling architectures and quantifies drug-induced pathway rewiring. Applied to MDA-MB-468 cells under three pharmacological conditions, SHP2 inhibition abolished PTPN11-mediated pathways and shifted first-hop effector distribution toward ERBB3 (21.5% to 25.2% of paths) and PIK3CA engagement (9.2% to 14.3% of paths), while SHP2 inhibitor washout revealed partial PTPN11 recovery with ERBB2 re-emerging as the dominant first-hop effector (30.3% of paths). This framework provides a systematic, reproducible approach for transforming time-resolved phosphoproteomic measurements into mechanistically interpretable signaling hypotheses, with direct applicabi

Matching Claidex post-mortems

1 of 1 indexed

May 22, 2026BG-60366 in EGFR-mutant NSCLC: a chimeric degrader retired after 33 patients in a saturated landscapeBG-60366SponsorMRS 16

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.