Beyond Oncogenes: Selectively Targeting Whole-Tumor Cell Growth Regulation.

Cell cycle-based surveillance system is an evolutionary adaptation aligned with the complex and heterogeneous nature of cancer in higher-order organisms and serves as a naturally existing model for potent anticancer therapy. It helps provide insights for the reasons underpinning the challenges facing oncogene-targeting in drug development, including cancer heterogeneity, difficulty in identifying "driver" oncogenes, and drug resistance due to additional mutations or other factors such as epigenetic changes, phenotypic adaptation, and microenvironmental influences. This perspective suggests the paradigm shift of targeting the whole cellular process instead of focusing on single-oncogene inhibition. Therefore, a potentially compelling strategy for cancer therapy is to selectively suppress tumor cells via targeting the whole-cell growth regulation while sparing normal cells. Future directions include precisely distinguishing and selectively interfering with tumor cell growth-regulatory networks from those of normally growing cells to achieve maximal clinical efficacy without compromising safety.