Pantziarka Pan, Blagden Sarah
The George Pantziarka TP53 Trust, London KT1 2JP, UK.
The Anti-Cancer Fund, Brusselsesteenweg 11, 1860 Meise, Belgium.
Cancers (Basel). 2022 Mar 23;14(7):1621. doi: 10.3390/cancers14071621.
The concept of the pre-cancerous niche applies the 'seed and soil' theory of metastasis to the initial process of carcinogenesis. TP53 is at the nexus of this process and, in the context of Li-Fraumeni Syndrome (LFS), is a key determinant of the conditions in which cancers are formed and progress. Important factors in the creation of the pre-cancerous niche include disrupted tissue homeostasis, cellular metabolism and chronic inflammation. While druggability of TP53 remains a challenge, there is evidence that drug re-purposing may be able to address aspects of pre-cancerous niche formation and thereby reduce the risk of cancer in individuals with LFS.
癌前生态位的概念将转移的“种子与土壤”理论应用于致癌作用的初始过程。TP53处于这一过程的核心位置,在李-佛美尼综合征(LFS)的背景下,它是癌症形成和进展条件的关键决定因素。癌前生态位形成的重要因素包括组织内稳态破坏、细胞代谢和慢性炎症。虽然TP53的可成药性仍然是一个挑战,但有证据表明,药物重新利用或许能够解决癌前生态位形成的相关问题,从而降低LFS患者患癌的风险。