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实体瘤与激酶抑制:管理与治疗疗效的演变。

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution.

机构信息

Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, Brazil.

Department of Pediatrics, Octávio Lobo Children's Hospital, Belém 60430-275, Brazil.

出版信息

Int J Mol Sci. 2022 Mar 30;23(7):3830. doi: 10.3390/ijms23073830.

Abstract

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients' prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones' survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host's immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.

摘要

全球癌症病例不断增加,某些肿瘤亚型的死亡率极高,这引发了人们的疑问,即当前的癌症管理方案是否有效,以及为改善肿瘤患者的预后已经采取了哪些措施。癌症治疗的传统化疗-免疫疗法方案侧重于使用能够克服肿瘤克隆生存机制并诱导细胞凋亡的细胞毒性药物,以及增强宿主免疫系统以阻止恶性细胞持续生长的能力。在过去的几十年中,为了避免传统化疗-免疫疗法的高度毒性作用,并克服肿瘤多药耐药性的出现,人们对精准医学和靶向分子疗法领域产生了越来越大的兴趣,尽管这些是肿瘤学实践中的相对较新的替代方案,但通过靶向分子疗法实现的更高的特异性和积极的临床结果已经使它们成为癌症管理未来的有希望的前景。近年来,作为酪氨酸激酶抑制剂的靶向药物的开发和应用使癌症治疗进入了特异性时代。此外,靶向治疗、免疫疗法和传统化疗的联合使用为许多恶性肿瘤的标准治疗带来了创新,为复发性肿瘤患者带来了新的希望。本文包含了过去 5 年中利用激酶抑制剂 (KIs) 作为单一疗法或与其他细胞毒性药物联合治疗实体瘤患者的一系列临床试验。报告了具有不同疗效程度的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda5/8998551/04e28c433074/ijms-23-03830-g001.jpg

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