靶向RTKs/nRTKs作为治疗三阴性乳腺癌的有希望的治疗策略:来自临床试验的证据

IF 16.7 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B Kunnumakkara
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引用次数: 0

摘要

广泛的异质性和有效靶向治疗的有限可用性导致三阴性乳腺癌(TNBC)的预后具有挑战性,生存期有限。最近的研究表明,多种酪氨酸激酶(TKs)在这种癌症中的异常表达,对肿瘤细胞的增殖、存活、侵袭和迁移有重要作用。鉴于TKs及其受体在肿瘤的发生、发展和进展中起着关键作用,当代向精准医学的范式转变突出了TKs及其受体作为针对一系列恶性肿瘤的药物治疗的有希望的靶点。深入的研究集中在各种单克隆抗体(mab)和小分子抑制剂上,这些抗体特异性靶向蛋白,如表皮生长因子受体(EGFR)、血管内皮生长因子受体(VEGF)、血管内皮生长因子受体(VEGFR)、细胞间充质上皮过渡因子(c-MET)、人表皮生长因子受体2 (HER2)等,用于对抗TNBC。这些药物已经在单药治疗和与其他化疗药物的联合治疗中进行了研究。尽管取得了这些进展,但在TK靶向治疗领域仍有大量未开发的潜力,有望重塑治疗前景。这篇综述总结了各种TK靶向治疗作为TNBC的潜在治疗干预措施,剖析了来自不同临床研究的结果和启示。综合临床试验得出的一个关键结论表明,无论是单独治疗还是联合治疗,为了获得TK靶向治疗的最大效率,有必要对tnbc进行深入的分子表征。此外,我们的观察结果强调了TNBC中TK靶向治疗的结果在很大程度上受到患者队列多样性的影响,强调了个体患者遗传/分子谱的优先性,以便为临床研究进行精确的TNBC患者分层。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.

The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.

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来源期刊
Military Medical Research
Military Medical Research Medicine-General Medicine
CiteScore
38.40
自引率
2.80%
发文量
485
审稿时长
8 weeks
期刊介绍: Military Medical Research is an open-access, peer-reviewed journal that aims to share the most up-to-date evidence and innovative discoveries in a wide range of fields, including basic and clinical sciences, translational research, precision medicine, emerging interdisciplinary subjects, and advanced technologies. Our primary focus is on modern military medicine; however, we also encourage submissions from other related areas. This includes, but is not limited to, basic medical research with the potential for translation into practice, as well as clinical research that could impact medical care both in times of warfare and during peacetime military operations.
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