Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, G. Narutowicza St 11/12, 80-233 Gdansk, Poland; Department of Medical Genetics, Institute of Clinical Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway.
Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, G. Narutowicza St 11/12, 80-233 Gdansk, Poland.
Drug Discov Today. 2024 Aug;29(8):104056. doi: 10.1016/j.drudis.2024.104056. Epub 2024 Jun 4.
As a global health challenge, cancer prompts continuous exploration for innovative therapies that are also based on new targets. One promising avenue is targeting the shelterin protein complex, a safeguard for telomeres crucial in preventing DNA damage. The role of shelterin in modulating ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) kinases, key players in the DNA damage response (DDR), establishes its significance in cancer cells. Disrupting these defence mechanisms of shelterins, especially in cancer cells, renders telomeres vulnerable, potentially leading to genomic instability and hindering cancer cell survival. In this review, we outline recent approaches exploring shelterins as potential anticancer targets, highlighting the prospect of developing selective molecules to exploit telomere vulnerabilities toward new innovative cancer treatments.
作为一个全球性的健康挑战，癌症促使人们不断探索创新疗法，这些疗法也基于新的靶点。一个有前途的途径是针对庇护蛋白复合物，该复合物是保护端粒的关键，端粒对于防止 DNA 损伤至关重要。庇护蛋白在调节共济失调毛细血管扩张突变（ATM）和共济失调毛细血管扩张和 Rad3 相关（ATR）激酶中的作用，这些激酶是 DNA 损伤反应（DDR）中的关键参与者，这表明其在癌细胞中的重要性。破坏庇护蛋白的这些防御机制，特别是在癌细胞中，会使端粒变得脆弱，可能导致基因组不稳定并阻碍癌细胞的存活。在这篇综述中，我们概述了最近探索庇护蛋白作为潜在抗癌靶点的方法，强调了开发选择性分子利用端粒弱点来开发新的创新癌症治疗方法的前景。
