Targeting oncogene-induced cellular plasticity for tumor therapy

Cellular plasticity, the remarkable adaptability of cancer cells to survive under various stress conditions, is a fundamental hallmark that significantly contributes to treatment resistance, tumor metastasis, and disease recurrence. Oncogenes, the driver genes that promote uncontrolled cell proliferation, have long been recognized as key drivers of cellular transformation and tumorigenesis. Paradoxically, accumulating evidence demonstrates that targeting certain oncogenes to inhibit tumor cell proliferation can unexpectedly induce processes like epithelial-to-mesenchymal transition (EMT), conferring enhanced invasive and metastatic capabilities. In this review, we summarize the latest models elucidating the biology of oncogenes that concurrently promote cell proliferation while inhibiting metastasis. We suggest that the complexity of oncogene-induced cellular plasticity, involving the participation of multiple signaling pathways and mechanisms, necessitates a multifaceted approach, prompting a shift towards precision targeting strategies that can effectively target oncogenes without exacerbating metastatic potential.