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PIM1 激酶及其在实体瘤中的多种底物。

PIM1 kinase and its diverse substrate in solid tumors.

机构信息

School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) Deemed-to-Be-University, Bhubaneswar, 751024, India.

出版信息

Cell Commun Signal. 2024 Nov 1;22(1):529. doi: 10.1186/s12964-024-01898-y.

Abstract

The PIM kinase family, consisting of PIM1, PIM2, and PIM3, is a group of serine/threonine protein kinases crucial for cellular growth, immunoregulation, and oncogenesis. PIM1 kinase is often overexpressed in solid and hematopoietic malignancies, promoting cell survival, proliferation, migration, and senescence by activating key genes. In vitro and in vivo studies have established the oncogenic potential of PIM1 kinases. These kinases have been implicated in tumor progression, metastasis, and resistance to chemotherapy, underscoring their potential as a therapeutic target for cancer therapy. This review delves into the intricate molecular mechanisms through which PIM1 interacts with specific substrates in different tumor tissues, leading to diverse outcomes in various human cancers. Over the past decade, the inhibition of PIM1 in cancers has garnered significant attention as a potential standalone treatment. Various in vitro, in vivo, and early clinical trial data have provided support for this approach to varying extents. Novel compounds that inhibit PIM1 kinase have shown effectiveness and a favorable toxicity profile in preclinical studies. Several of these substances are now being studied in clinical trials due to their promising outcomes. This article provides a thorough examination of the PIM1 kinase pathways and the recent advancements in producing PIM1 kinase inhibitors for the treatment of cancer.

摘要

PIM 激酶家族由 PIM1、PIM2 和 PIM3 组成,是一组丝氨酸/苏氨酸蛋白激酶,对于细胞生长、免疫调节和肿瘤发生至关重要。PIM1 激酶在实体瘤和血液恶性肿瘤中常常过表达,通过激活关键基因促进细胞存活、增殖、迁移和衰老。体外和体内研究已经确立了 PIM1 激酶的致癌潜力。这些激酶与肿瘤进展、转移和化疗耐药性有关,强调了它们作为癌症治疗的治疗靶点的潜力。这篇综述深入探讨了 PIM1 与不同肿瘤组织中特定底物相互作用的复杂分子机制,导致各种人类癌症的不同结果。在过去的十年中,抑制癌症中的 PIM1 作为一种潜在的独立治疗方法引起了极大的关注。各种体外、体内和早期临床试验数据在不同程度上为这种方法提供了支持。在临床前研究中,几种抑制 PIM1 激酶的新型化合物显示出有效性和良好的毒性特征。由于这些物质有很好的效果,目前正在临床试验中进行研究。本文全面研究了 PIM1 激酶途径以及为治疗癌症而开发的 PIM1 激酶抑制剂的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11531143/a5cc99311aa4/12964_2024_1898_Fig1_HTML.jpg

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