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整合素作为癌症治疗的新靶点。

Integrins as A New Target for Cancer Treatment.

机构信息

Department of Medical and Experimental Oncology, Heliodor Swiecicki University Hospital, Poznan University of Medical Sciences, Poznan, Poland.

Department of Biology and Environmental Studies, University of Medical Sciences, Poznan, Poland.

出版信息

Anticancer Agents Med Chem. 2019;19(5):580-586. doi: 10.2174/1871520618666181119103413.

Abstract

Despite the great progress in the development of targeted therapies for different types of cancer utilizing monoclonal antibodies (e.g., cetuximab for colorectal cancer and head and neck cancer therapy), kinase inhibitors (e.g., sorafenib for kidney cancer and gastrointestinal stromal tumours therapy), and immunomodulatory treatments (e.g., nivolumab and pembrolizumab for melanoma therapy and lung cancer therapy), there is still a need to search for new, more effective treatments. Integrins are responsible for intercellular adhesion and interaction with the cellular matrix. The function of integrins is related to the transduction of intracellular signals associated with adhesion, migration, cell proliferation, differentiation, and apoptosis. Molecules targeting integrins that lead to cancer cell death have been developed. The most advanced molecules studied in clinical trials are abituzumab, intetumumab and cilengitide. There are different groups of anti-integrin drugs: monoclonal antibodies (e.g., abituzumab) and other such as cilengitide, E7820 and MK-0429. These drugs have been evaluated in various cancer types. However, they have shown modest efficacy, and none of them have yet been approved for cancer treatment. Studies have shown that patient selection using biomarkers might improve the efficacy of anti-integrin cancer treatment. Many preclinical models have demonstrated promising results using integrin visualization for cancer detection and treatment efficacy monitoring; however, these strategies require further evaluation in humans.

摘要

尽管在利用单克隆抗体(例如,西妥昔单抗用于结直肠癌和头颈部癌症治疗)、激酶抑制剂(例如,索拉非尼用于肾癌和胃肠道间质瘤治疗)和免疫调节治疗(例如,纳武单抗和派姆单抗用于黑色素瘤和肺癌治疗)开发针对不同类型癌症的靶向治疗方面取得了巨大进展,但仍需要寻找新的、更有效的治疗方法。整合素负责细胞间黏附和与细胞基质的相互作用。整合素的功能与与黏附、迁移、细胞增殖、分化和凋亡相关的细胞内信号转导有关。已经开发出了针对导致癌细胞死亡的整合素的分子。在临床试验中研究最先进的分子是阿比特珠单抗、英特珠单抗和西仑吉肽。有不同类型的抗整合素药物:单克隆抗体(例如,阿比特珠单抗)和其他药物,如西仑吉肽、E7820 和 MK-0429。这些药物已在各种癌症类型中进行了评估。然而,它们的疗效有限,尚未被批准用于癌症治疗。研究表明,使用生物标志物进行患者选择可能会提高抗整合素癌症治疗的疗效。许多临床前模型已经证明了通过整合素可视化用于癌症检测和治疗效果监测的有前途的结果;然而,这些策略需要在人类中进一步评估。

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