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.
近期在健康组织中鉴定出致癌细胞，以及在尸检中偶然发现的高发性惰性癌症，揭示了肿瘤发生机制比以往认知更为复杂。人体由约200种不同类型的40万亿个细胞组成，这些细胞精密排列于复杂的三维基质中，因此需要完善的抑制机制来遏制具有致死潜能的恶性细胞异常增殖。理解这种防御机制如何被突破从而引发肿瘤发生，以及为何在细胞层面上癌症发生率极低，对未来预防治疗至关重要。本综述将探讨早期癌变细胞如何被抑制进一步恶化的机制，以及癌症风险因素通过非突变通路促进肿瘤生长的途径。从本质上说，由于不涉及永久性基因组改变，这些促癌机制可能成为临床靶向干预的突破口。最后，我们评估了现有早期癌症干预策略，并对分子癌症预防的后续研究方向提出展望。
肿瘤(癌症)患者之家