Current concepts and new insights into early tumor initiation

Despite substantial research and clinical efforts, the mechanisms underlying tumor initiation and progression remain incompletely understood and, in some areas, controversial. In tumorigenesis, genetic mutations and abnormal gene expression can confer survival advantages on selected cells and contribute to reciprocal interactions with the tumor microenvironment (TME), thereby promoting malignant transformation. This process includes the progression from a precancerous lesion to primary cancer. To maintain their survival advantage, cancerous cells must progressively optimize and exploit the existing functions and regulatory systems of all tissue cells and maximize the body’s available resources. Exploiting existing physiological systems and resources supports the clonal expansion and high dominance of tumor cells after their formation, allowing tumor cells to proliferate and infiltrate adjacent tissue. Temporally, tumor cells exhibit the growth and change characteristics of ‘persistent dynamic biology’ and dynamically update themselves. The patient-specific TME is the basis of cancer recurrence and metastasis. In addition, we propose the “Dysregulated Adaptive Cascade Model” (DACM) to elucidate the early processes of tumorigenesis. Incorporating these different perspectives will enormously refresh our understanding of tumorigenesis. Conventional cancer-control strategies emphasize early detection, early diagnosis, and early treatment, but they do not fully address prevention at the precancerous stage. Therefore, we propose new cancer prevention principles: early detection of precancerous lesions, early determination of patient-specific TME, and early intervention to halt tumorigenesis. These new cancer prevention principles are of great significance to the prevention and control of the occurrence and development of tumors. In conclusion, the highlights of this article include: (i) proposing the novel “persistent dynamic biology” concept and the early tumorigenesis model DACM; (ii) establishing an integrated framework of the above concept and organoid culture for individualized cancer detection, diagnosis, and treatment; and (iii) proposing three innovative cancer prevention principles targeting precancerous lesions, patient-specific TME, and early intervention.