IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
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引用次数: 0

摘要

Gsα编码的GNAS外显子发生突变,即俗称的gsp癌基因,是所有参与肿瘤发生的异三聚体G蛋白中最常见的突变。GNAS R201 是最常见的突变,其次是 Q227,主要见于 IPMN、垂体、甲状腺、阑尾、结直肠等各种肿瘤和癌症。本综述强调了 gsp 致癌基因的关键意义及其对 GNAS 突变持续成瘾的影响。最近的研究阐明了复杂的机理,为致癌基因 GNAS 对肿瘤形成、发展和维持的深远影响提供了确凿的证据。我们发现 Gsα 是疫苗疗法、等位基因特异性抑制剂和基于环肽的 G 蛋白小分子抑制剂的理想候选新抗原,并利用这些发现探索了直接靶向致癌 GNAS 的治疗潜力。此外,还讨论了减轻 GNAS 基因突变影响的替代治疗方法和以患者为中心的研究。重点阐述了旨在解决这些靶向 GNAS 激活突变的方法所固有的潜在挑战的新型研究和策略,以及进一步调查的可能途径。这篇综述旨在反响目前对 GNAS 致癌潜力、GNAS 驱动的肿瘤和癌症的基因组和生物学特征以及针对它们的潜在治疗策略的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Contract to kill: GNAS mutation
The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα as an ideal neoantigen candidate for vaccine therapy, allele-specific inhibitors, and cyclic peptide-based small molecular inhibitors for G proteins and explored the therapeutic potential to target oncogenic GNAS directly. Alternative therapeutic modalities and patient-centric studies to mitigate the impact of GNAS mutations are also discussed. The exposition of novel studies and strategies designed to address the potential challenges inherent in these approaches of targeting the activating mutations of GNAS, along with probable avenues for further investigation, are highlighted. This review aims to reverberate the current understanding of the oncogenic potential of GNAS, the genomic and biological landscape of GNAS-driven neoplasms and cancers, and potential therapeutic strategies against them.
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来源期刊
Molecular Cancer
Molecular Cancer 医学-生化与分子生物学
CiteScore
54.90
自引率
2.70%
发文量
224
审稿时长
2 months
期刊介绍: Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.
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