RESUMO
This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.
Assuntos
Neoplasias , Telômero , Proteína 1 de Ligação a Repetições Teloméricas , Proteína 2 de Ligação a Repetições Teloméricas , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/terapia , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/genética , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/genética , Telômero/metabolismo , Terapia de Alvo Molecular/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Complexo Shelterina , Proteínas de Ligação a TelômerosRESUMO
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.