Convergent and Divergent Signaling Pathways in Cancer: A Dual-Axis Model for Adaptive Precision Oncology

Despite significant advances in cancer research, the complexity of signaling pathways remains a major challenge in precision oncology. Tumors harbor a diverse array of genetic alterations; however, these often converge onto a limited set of core signaling pathways, notably RAS/RAF/MEK/ERK (MAPK), PI3K/AKT/mTOR (PAM), and Wnt/β-catenin. Concurrently, these pathways diverge extensively downstream, driving therapeutic resistance through mechanisms such as epithelial-mesenchymal transition, immune evasion, and metabolic reprogramming. Unlike previous literature that largely provides descriptive accounts of pathway alterations, this review uniquely synthesizes convergent and divergent signaling into a clinically actionable diagnostic and therapeutic framework. It critically assesses current precision oncology strategies, identifies gaps, and proposes a dual-axis model that integrates static genomic profiling with dynamic signaling evolution to inform precision therapy. By highlighting opportunities for combination therapy informed by pathway interdependencies and adaptive resistance mechanisms, this perspective provides novel clinical insights and tangible directions for future research in overcoming resistance in cancer treatment.