TARGETED PROTEIN DEGRADATION WITH PROTACS IN CANCER THERAPY: MECHANISMS, CLINICAL ADVANCES, CHALLENGES, AND FUTURE PERSPECTIVES

Targeted protein degradation (TPD) has emerged as one of the most transformational approaches in current drug development, fundamentally challenging the long-standing assumption that small compounds must only inhibit their protein targets. Among TPD methods, proteolysis-targeting chimeras (PROTACs) have attracted considerable attention from both academic researchers and clinicians, giving a catalytic mechanism that permits the total removal of disease-driving proteins rather than just reducing their activity. This thorough analysis investigates the molecular basis of PROTAC technology, tracking its progression from an elegant intellectual notion to a clinically approved treatment platform. We discuss the molecular machinery of the ubiquitin - proteas ome system that PROTACs exploit, analyze the structural design principles underlying effective degrader molecules, and provide a detailed survey of the current clinical landscape,including the landmark progression of vepdegestrant (ARV-471) through Phase III clinical evaluation, culminating in U.S. Food and Drug Administration (FDA) approval on May 1, 2026.