探索联合靶向表皮生长因子受体和纺锤体组装检查点途径对口腔癌的治疗意义

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmaceutics Pub Date : 2024-09-11 DOI:10.3390/pharmaceutics16091196
Mafalda Calheiros-Lobo, João P. N. Silva, Bárbara Pinto, Luís Monteiro, Patrícia M. A. Silva, Hassan Bousbaa
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引用次数: 0

摘要

头颈癌(HNC)是全球第六大常见癌症,发病率呈上升趋势,其中以口腔鳞状细胞癌(OSCC)为主要亚型。口腔鳞状细胞癌主要影响中老年男性,通常发生在舌后外侧缘,会导致严重的毁容和功能障碍,如吞咽和语言障碍。尽管人们对 OSCC 的遗传和表观遗传变异有了更深入的了解,但晚期患者的存活率仍然很低,这凸显了对新治疗方案的需求。主要治疗方法包括手术,通常结合放疗(RT)和化疗(CT)。以西妥昔单抗为基础的化疗靶向80-90%的HNC中过表达的表皮生长因子受体(EGFR),是常用的化疗方法,但与不良预后相关。此外,单轴纺锤体 1(MPS1)是纺锤体组装检查点(SAC)的一个组成部分,由于其在有丝分裂过程中对基因组保真度的作用以及在多种癌症中的过度表达,它也是一个重要的靶点。这篇综述探讨了表皮生长因子受体和 MPS1 作为 HNC 的治疗靶点,分析了它们的分子机制以及抑制它们对癌细胞的影响。它还强调了微管靶向药物(MTAs)和抗有丝分裂药物等组合方法在改善 HNC 治疗、患者预后和生存率方面的前景。
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Exploring the Therapeutic Implications of Co-Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer
Head and neck cancer (HNC), the sixth most common cancer worldwide, is increasing in incidence, with oral squamous cell carcinoma (OSCC) as the predominant subtype. OSCC mainly affects middle-aged to elderly males, often occurring on the posterior lateral border of the tongue, leading to significant disfigurement and functional impairments, such as swallowing and speech difficulties. Despite advancements in understanding OSCC’s genetic and epigenetic variations, survival rates for advanced stages remain low, highlighting the need for new treatment options. Primary treatment includes surgery, often combined with radiotherapy (RT) and chemotherapy (CT). Cetuximab-based chemotherapy, targeting the overexpressed epidermal growth factor receptor (EGFR) in 80–90% of HNCs, is commonly used but correlates with poor prognosis. Additionally, monopolar spindle 1 (MPS1), a spindle assembly checkpoint (SAC) component, is a significant target due to its role in genomic fidelity during mitosis and its overexpression in several cancers. This review explores EGFR and MPS1 as therapeutic targets in HNC, analyzing their molecular mechanisms and the effects of their inhibition on cancer cells. It also highlights the promise of combinatorial approaches, such as microtubule-targeting agents (MTAs) and antimitotic agents, in improving HNC therapies, patient outcomes, and survival rates.
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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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