Proteomics in Antitumor Drug Target Discovery, Toxicity, Resistance, and Precision Oncology

Proteomics, the comprehensive study of protein expression, localization, and modifications, has evolved from a fundamental research tool into a key complementary layer to genomics in antitumor drug development and precision oncology. This review highlights its multi-dimensional applications, including differential, chemical, and post-translational modification proteomics, for drug-target discovery and mechanism-of-action elucidation. It further discusses proteomics strategies, such as mass spectrometry-based quantitative approaches, protein microarray and single-cell proteomics, which enable the profiling of adverse drug reactions, the dissection of resistance mechanisms, and the advancement of precision oncology. To date, the translational maturity of these applications is uneven: proteomic biomarkers have entered prospective trials and informed molecular tumor board recommendations in selected Clinical Laboratory Improvement Amendments (CLIA) certified settings, whereas de novo proteomics-derived drug targets remain largely at the preclinical stage. By bridging basic research and clinical practice, proteomics provides a scientific framework that facilitates drug development and informs clinical translation.