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靶向癌症中的新抗原:乳腺癌的可能性与机遇

Targeting Neoantigens in Cancer: Possibilities and Opportunities in Breast Cancer.

作者信息

Chaudhry Zuhair, Boyadzhyan Anik, Sasaninia Kayvan, Rai Vikrant

机构信息

Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.

出版信息

Antibodies (Basel). 2024 Jun 10;13(2):46. doi: 10.3390/antib13020046.

Abstract

As one of the most prevalent forms of cancer worldwide, breast cancer has garnered significant attention within the clinical research setting. While traditional treatment employs a multidisciplinary approach including a variety of therapies such as chemotherapy, hormone therapy, and even surgery, researchers have since directed their attention to the budding role of neoantigens. Neoantigens are defined as tumor-specific antigens that result from a multitude of genetic alterations, the most prevalent of which is the single nucleotide variant. As a result of their foreign nature, neoantigens elicit immune responses upon presentation by Major Histocompatibility Complexes I and II followed by recognition by T cell receptors. Previously, researchers have been able to utilize these immunogenic properties and manufacture neoantigen-specific T-cells and neoantigen vaccines. Within the context of breast cancer, biomarkers such as tumor protein 53 (TP53), Survivin, Partner and Localizer of BRCA2 (PALB2), and protein tyrosine phosphatase receptor T (PTPRT) display exceeding potential to serve as neoantigens. However, despite their seemingly limitless potential, neoantigens must overcome various obstacles if they are to be fairly distributed to patients. For instance, a prolonged period between the identification of a neoantigen and the dispersal of treatment poses a serious risk within the context of breast cancer. Regardless of these current obstacles, it appears highly promising that future research into neoantigens will make an everlasting impact on the health outcomes within the realm of breast cancer. The purpose of this literature review is to comprehensively discuss the etiology of various forms of breast cancer and current treatment modalities followed by the significance of neoantigens in cancer therapeutics and their application to breast cancer. Further, we have discussed the limitations, future directions, and the role of transcriptomics in neoantigen identification and personalized medicine. The concepts discussed in the original and review articles were included in this review article.

摘要

作为全球最常见的癌症形式之一,乳腺癌在临床研究领域备受关注。传统治疗采用多学科方法,包括化疗、激素治疗甚至手术等多种疗法,但此后研究人员将注意力转向了新抗原的新兴作用。新抗原被定义为肿瘤特异性抗原,由多种基因改变产生,其中最常见的是单核苷酸变异。由于其外来性质,新抗原在由主要组织相容性复合体I和II呈递后引发免疫反应,随后被T细胞受体识别。此前,研究人员已经能够利用这些免疫原性特性制造新抗原特异性T细胞和新抗原疫苗。在乳腺癌背景下,诸如肿瘤蛋白53(TP53)、生存素、乳腺癌2号基因伴侣和定位蛋白(PALB2)以及蛋白酪氨酸磷酸酶受体T(PTPRT)等生物标志物作为新抗原显示出巨大潜力。然而,尽管新抗原似乎具有无限潜力,但如果要公平地分配给患者,它们必须克服各种障碍。例如,在乳腺癌背景下,从识别新抗原到治疗扩散之间的长时间间隔带来了严重风险。尽管存在这些当前障碍,但对新抗原的未来研究似乎极有希望对乳腺癌领域的健康结果产生持久影响。这篇文献综述的目的是全面讨论各种形式乳腺癌的病因和当前治疗方式,随后阐述新抗原在癌症治疗中的重要性及其在乳腺癌中的应用。此外,我们还讨论了局限性、未来方向以及转录组学在新抗原识别和个性化医学中的作用。原始文章和综述文章中讨论的概念都包含在这篇综述文章中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0087/11200483/5ee68610fbd0/antibodies-13-00046-g001.jpg

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