CDCP1 (CUB domain-containing protein 1) is a type I transmembrane glycoprotein that functions as an oncogenic signaling hub in multiple malignancies 1. Structurally, CDCP1 is a cell surface receptor that undergoes proteolytic cleavage by extracellular proteases, generating unique neoepitopes 2. Mechanistically, CDCP1 coordinates multiple tumorigenic signaling cascades including SRC/PKCδ, PI3K/AKT, WNT, and RAS/ERK pathways, while also modulating immune responses through CD6-mediated JAK/STAT pathway inhibition 13. In cancer biology, CDCP1 is overexpressed across diverse malignancies—breast, lung, colorectal, ovarian, kidney, liver, pancreatic, and hematopoietic cancers—with elevated levels associated with progressive disease and poor survival 14. CDCP1 overexpression correlates with metastatic potential, treatment resistance, and immune suppression through reduced CD8+ T cell cytotoxicity 35. Clinically, CDCP1 represents a dual-purpose biomarker and therapeutic target. It enables personalized cancer detection via PET imaging using radiolabeled anti-CDCP1 antibodies and supports targeted therapy through antibody-drug conjugates, bispecific T cell engagers, and radiotherapy 67. Combined targeting of CDCP1 with conventional therapies demonstrates synergistic efficacy, particularly in HER2+ breast cancers and treatment-resistant prostate cancer 87.