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酪氨酸激酶抑制剂作为下一代肿瘤治疗药物:当前策略、局限性和未来展望。

Tyrosine kinase inhibitors as next generation oncological therapeutics: Current strategies, limitations and future perspectives.

机构信息

Translational Pharmaceutics Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Telangana 500078, India.

Nanomedicine and Bioengineering Research Laboratory, Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak 484886, India.

出版信息

Therapie. 2022 Jul-Aug;77(4):425-443. doi: 10.1016/j.therap.2021.10.010. Epub 2021 Nov 2.

DOI:10.1016/j.therap.2021.10.010
PMID:34823895
Abstract

Protein kinases, a class of enzymes that govern various biological phenomena at a cellular level, are responsible for signal transduction in cells that regulate cellular proliferation, differentiation, and growth. Protein kinase enzyme mutation results in abnormal cell division leading to a pathological condition like cancer. Tyrosine kinase (TK) inhibitors, which helps as a potential drug candidate for the treatment of cancer, are continuously being developed. Majority of these drug candidates are being administered as conventional oral dosage form, which provides limited safety and efficacy due to non-specific delivery and uncontrolled biodistribution resulting into the adverse effects. A controlled drug delivery approach for the delivery of TK inhibitors may be a potential strategy with significant safety and efficacy profile. Novel drug delivery strategies provide target-specific drug delivery, improved pharmacokinetic behaviour, and sustained release leading to lower doses and dosing frequency with significantly reduced side effects. Along with basic aspects of tyrosine kinase, this review discusses various aspects related to the application of tyrosine kinase inhibitors in clinical oncological setting. Furthermore, the limitations/challenges and formulation advancements related to this class of candidates particularly for cancer management have been reviewed. It is expected that innovations in drug delivery approaches for TK inhibitors using novel techniques will surely provide a new insights for improved cancer treatment and patients' life quality.

摘要

蛋白激酶是一类在细胞水平上控制各种生物现象的酶,负责调节细胞增殖、分化和生长的细胞信号转导。蛋白激酶酶的突变导致异常的细胞分裂,导致癌症等病理状况。酪氨酸激酶 (TK) 抑制剂作为癌症治疗的潜在药物候选物不断被开发。这些药物候选物中的大多数被作为常规口服剂型给药,由于非特异性递送和不受控制的生物分布导致安全性和疗效有限,从而导致不良反应。用于 TK 抑制剂递送的控释药物递送方法可能是一种具有显著安全性和疗效特征的潜在策略。新型药物递送策略提供了靶向药物递送、改善的药代动力学行为和持续释放,从而降低剂量和给药频率,并显著减少副作用。除了酪氨酸激酶的基本方面,本综述还讨论了酪氨酸激酶抑制剂在临床肿瘤学中的应用的各个方面。此外,还综述了与该类候选物相关的局限性/挑战和制剂进展,特别是用于癌症管理。预计使用新型技术的 TK 抑制剂药物递送方法的创新将为改善癌症治疗和患者生活质量提供新的思路。

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Tyrosine kinase inhibitors as next generation oncological therapeutics: Current strategies, limitations and future perspectives.酪氨酸激酶抑制剂作为下一代肿瘤治疗药物:当前策略、局限性和未来展望。
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