最近在健康组织中鉴定了致癌细胞，以及在尸检中偶然发现的渐进性癌症的普遍存在，揭示了肿瘤起始的复杂性比之前认为的更加复杂。人体内含有大约200种不同类型的约40万亿个细胞，这些细胞组成了一个复杂的三维矩阵，在遏制具有杀伤力的恶性细胞的异常生长方面需要精致的机制。了解如何克服这种防御来触发肿瘤发生，以及为什么癌症在细胞水平上非常罕见，对未来的预防治疗至关重要。在本综述中，我们讨论了早期启动细胞如何受到进一步肿瘤发生的保护，以及癌症风险因素促进肿瘤生长的非诱变通路。从本质上讲，永久基因组改变的缺失使这些促进肿瘤的机制在临床上成为可靶向的。最后，我们考虑了早期癌症拦截的现有策略，并展望了分子癌症预防的下一步步骤。Copyright © 2023 Elsevier Inc. All rights reserved.

Recent identification of oncogenic cells within healthy tissues and the prevalence of indolent cancers found incidentally at autopsies reveal a greater complexity in tumor initiation than previously appreciated. The human body contains roughly 40 trillion cells of 200 different types that are organized within a complex three-dimensional matrix, necessitating exquisite mechanisms to restrain aberrant outgrowth of malignant cells that have the capacity to kill the host. Understanding how this defense is overcome to trigger tumorigenesis and why cancer is so extraordinarily rare at the cellular level is vital to future prevention therapies. In this review, we discuss how early initiated cells are protected from further tumorigenesis and the non-mutagenic pathways by which cancer risk factors promote tumor growth. By nature, the absence of permanent genomic alterations potentially renders these tumor-promoting mechanisms clinically targetable. Finally, we consider existing strategies for early cancer interception with perspectives on the next steps for molecular cancer prevention.Copyright © 2023 Elsevier Inc. All rights reserved.