Protacs in cancer therapy: mechanisms, design, clinical trials, and future directions.

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2025-06-01 Epub Date: 2024-11-29 DOI:10.1007/s13346-024-01754-z
Akash Vikal, Rashmi Maurya, Brij Bihari Patel, Rajeev Sharma, Preeti Patel, Umesh K Patil, Balak Das Kurmi
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引用次数: 0

Abstract

Cancer develops as a result of changes in both genetic and epigenetic mechanisms, which lead to the activation of oncogenes and the suppression of tumor suppressor genes. Despite advancements in cancer treatments, the primary approach still involves a combination of chemotherapy, radiotherapy, and surgery, typically providing a median survival of approximately five years for patients. Unfortunately, these therapeutic interventions often bring about substantial side effects and toxicities, significantly impacting the overall quality of life for individuals undergoing treatment. Therefore, urgent need of research required which comes up with effective treatment of cancer. This review explores the transformative role of Proteolysis-Targeting Chimeras (PROTACs) in cancer therapy. PROTACs, an innovative drug development strategy, utilize the cell's protein degradation machinery to selectively eliminate disease-causing proteins. The review covers the historical background, mechanism of action, design, and structure of PROTACs, emphasizing their precision in targeting oncogenic proteins. The discussion extends to the challenges, nanotechnology applications, and ongoing clinical trials, showcasing promising results and clinical progress. The review concludes with insights into patents, future directions, and the potential impact of PROTACs in addressing dysregulated protein expression across various diseases. Overall, it provides a concise yet comprehensive overview for researchers, clinicians, and industry professionals involved in developing targeted therapies.

质子在癌症治疗中的作用:机制、设计、临床试验和未来方向。
癌症的发展是由于遗传和表观遗传机制的变化,导致致癌基因的激活和肿瘤抑制基因的抑制。尽管癌症治疗取得了进步,但主要的方法仍然包括化疗、放疗和手术的结合,通常为患者提供大约5年的中位生存期。不幸的是,这些治疗干预常常带来严重的副作用和毒性,严重影响接受治疗的个体的整体生活质量。因此,迫切需要研究出有效的癌症治疗方法。本文综述了靶向蛋白水解嵌合体(Proteolysis-Targeting Chimeras, PROTACs)在癌症治疗中的变革性作用。PROTACs是一种创新的药物开发策略,利用细胞的蛋白质降解机制选择性地消除致病蛋白质。本文综述了PROTACs的历史背景、作用机制、设计和结构,重点介绍了其靶向癌原蛋白的精确性。讨论扩展到挑战、纳米技术应用和正在进行的临床试验,展示了有希望的结果和临床进展。该综述总结了PROTACs在解决各种疾病中蛋白表达失调方面的专利、未来方向和潜在影响。总的来说,它为研究人员、临床医生和参与开发靶向治疗的行业专业人士提供了一个简明而全面的概述。
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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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