Abstract

Oncological diseases have always been among the most significant pathologies. Therefore, development of effective antitumor drugs is considered one of the priorities of modern healthcare. Inhibitors of proteins, enzymes, and receptors that regulate the signaling pathways of tumor cells, as well as apoptosis inductors, are used for tumor chemotherapy. The most significant and studied signaling pathways are the Raf/MEK/ERK and phosphoinositide-3 kinase (PI3K). Changes in the cascades of these pathways lead to the modulation of many cellular functions, such as cell growth and survival, proliferation, differentiation, and adhesion. These signaling cascades are closely related to Ras proteins. Oncogenic forms of Ras proteins are detected in a large number of tumor diseases—more than 30% of all forms of neoplasms. The literature data of the last 30 years on the study of the key stages of signaling cascades initiated by oncogenic Ras proteins are considered in this review. The processing features of Ras proteins, which are currently considered as promising molecular targets for the development of antitumor drugs, are analyzed separately. Literature data on new strategies to search for effective antineoplastic agents, which are based on Ras proteins signaling pathways, and bipharmacophore compounds are presented and discussed.

中文翻译：

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基于Ras蛋白信号级联的抗肿瘤药物设计分子靶标

摘要

肿瘤疾病一直是最重要的病理之一。因此，开发有效的抗肿瘤药物被认为是现代医疗保健的重点之一。调节肿瘤细胞信号传导途径的蛋白质，酶和受体的抑制剂以及凋亡诱导剂被用于肿瘤化学疗法。最重要且已研究的信号传导途径是Raf / MEK / ERK和磷酸肌醇3激酶（PI3K）。这些途径的级联变化导致许多细胞功能的调节，例如细胞生长和存活，增殖，分化和粘附。这些信号级联与Ras蛋白密切相关。在多种肿瘤疾病中检测到Ras蛋白的致癌形式，占所有形式肿瘤的30％以上。本文回顾了最近30年有关致癌Ras蛋白引发的信号级联关键阶段研究的文献数据。Ras蛋白的加工特性（目前被认为是开发抗肿瘤药物的有希望的分子靶标）将单独进行分析。提出并讨论了有关基于Ras蛋白信号传导途径和双药效团化合物寻找有效抗肿瘤药的新策略的文献资料。