Vikal Akash, Maurya Rashmi, Patel Brij Bihari, Sharma Rajeev, Patel Preeti, Patil Umesh K, Das Kurmi Balak
Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga, 142001, Punjab, India.
Department of Respiratory Medicine, School of Excellence in Pulmonary Medicines, Netaji Subhash Chandra Bose Medical College, Jabalpur, 482003, Madhya Pradesh, India.
Drug Deliv Transl Res. 2025 Jun;15(6):1801-1827. doi: 10.1007/s13346-024-01754-z. Epub 2024 Nov 29.
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.
癌症是由遗传和表观遗传机制的变化引起的,这些变化导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展,但主要方法仍然是化疗、放疗和手术相结合,通常为患者提供约五年的中位生存期。不幸的是,这些治疗干预措施往往会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,迫切需要开展研究以找到有效的癌症治疗方法。本综述探讨了蛋白酶靶向嵌合体(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。综述涵盖了PROTACs的历史背景、作用机制、设计和结构,强调了它们在靶向致癌蛋白方面的精确性。讨论还涉及挑战、纳米技术应用和正在进行的临床试验,展示了有前景的结果和临床进展。综述最后对专利、未来方向以及PROTACs在解决各种疾病中蛋白质表达失调方面的潜在影响进行了深入探讨。总体而言,它为参与开发靶向治疗的研究人员、临床医生和行业专业人士提供了简洁而全面的概述。