Semiconductor‐Enhanced Raman Spectroscopy for Cancer Biomarker Sensors: Where We Stand and Where We Are Going at the 50th Anniversary

ABSTRACT Cancer remains a leading global cause of mortality, primarily due to the lack of reliable early detection methods for cancer biomarkers. Conventional techniques (e.g., enzyme‐linked immunosorbent assay (ELISA), polymerase chain reaction (PCR)) are limited by insufficient sensitivity and high complexity, while plasmonic noble metal‐based surface‐enhanced Raman spectroscopy (SERS‐I) suffers from poor stability, biotoxicity, and high cost. This review focuses on semiconductor‐based surface‐enhanced Raman spectroscopy (SERS‐II) as a robust alternative for cancer biomarker detection. This spectroscopy relies mainly on chemical enhancement (via charge transfer between semiconductors and analytes) with auxiliary electromagnetic enhancement, overcoming plasmonic noble metal drawbacks. Key SERS‐II substrates include metal oxides (e.g., CuO, Fe ₂ O ₃ , TiO _2, and ZnO), perovskites, 2D semiconductors (e.g., MoS ₂ and MXenes), and organic semiconductors, each offering unique advantages like stability, dual‐mode detection, or biocompatibility. The applications of SERS‐II in cancer biomarker detection cover ex situ sensing and in situ monitoring, targeting nucleic acids, proteins, CTCs, and tumor‐associated bacteria. Despite challenges (substrate stability, reproducibility), future advances (novel semiconductors, artificial intelligence (AI) integration, and clinical standardization) will solidify SERS‐II's role in precision oncology.