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精准诊断和治疗三阴性乳腺癌的进展:利用 CRISPR-Cas 和工程 CAR T 细胞介导的治疗方法的诊断潜力。

Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

机构信息

Indian Council of Agricultural Research- National Institute on Foot and Mouth Disease- International Center for Foot and Mouth Disease, Bhubaneswar, Odisha, India.

Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi-Mumbai 410210, India.

出版信息

Environ Res. 2023 Oct 15;235:116573. doi: 10.1016/j.envres.2023.116573. Epub 2023 Jul 15.

DOI:10.1016/j.envres.2023.116573
PMID:37437865
Abstract

Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.

摘要

癌症的特征是细胞生长失控、调控途径紊乱以及遗传突变的积累。不同类型癌症的这些突变导致信号通路的中断和与细胞生长和增殖相关的蛋白质表达的改变。本综述强调了 AKT 信号级联和视网膜母细胞瘤蛋白 (pRb) 调节级联作为新型纳米治疗干预的有前途的靶点。通过将最先进的基因编辑工具(如簇状规则间隔短回文重复序列 (CRISPR)-Cas 系统)与纳米材料和靶向 AKT 协同作用,有可能显著提高癌症诊断水平。此外,将经过修饰的 CAR-T 细胞整合到多功能纳米递药系统中为靶向癌症抑制提供了一种很有前途的方法,包括消除癌症干细胞 (CSCs)。在高度侵袭性和转移性三阴性乳腺癌 (TNBC) 的背景下,本综述特别关注设计创新的纳米治疗方法。对于 TNBC 的临床前和临床检测,利用 CRISPR-Cas 系统,由 RNA (gRNA) 指导,并与专门设计用于检测 TNBC 突变序列的荧光报告子结合,可能具有前景。此外,一种涉及 TNBC 特异性 iCAR 和 syn-Notch CAR T 细胞工程的前沿方法,与共递送一种包含针对 CSCs 的条件复制腺病毒载体 (CRAdV) 的杂交聚合物纳米脂质体联合使用,可能是一种有趣的干预策略。因此,本综述为 TNBC 及其他癌症的纳米治疗领域的令人兴奋的进展铺平了道路。

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