解读化疗耐药的关键特征:乳腺癌研究中的蛋白质组学故事。

IF 8.3
Praneeta Pradip Bhavsar, Bhargab Kalita, Khushman Taunk, Srikanth Rapole
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引用次数: 0

摘要

化疗耐药是指复杂的、多因素的分子机制,恶性细胞破坏化疗药物的细胞毒性,从而阻碍治疗效果。这种现象是通过一系列过程的融合而精心策划的,我们认为这是癌症化疗耐药的主要标志。药物转运体的失调、促生存途径的激活、癌症干细胞驱动的增殖、DNA损伤和修复机制、逃避细胞凋亡、诱导自噬、细胞外囊泡的分泌和代谢重编程是癌症化疗耐药的主要机制。乳腺癌是最常见和最具侵袭性的癌症类型之一,由于其异质性,在治疗方面面临重大挑战。尽管各种治疗方案取得了进展,但化疗耐药仍然是有效管理乳腺癌的重大挑战。在这种情况下,高通量蛋白质组学方法,定量评估蛋白质组范围内的改变和探索翻译后修饰,可以为揭示化疗耐药性的分子复杂性提供一个公正的框架。本文综述了先进的蛋白质组学技术在阐明乳腺癌化疗耐药病理生理机制方面的应用。此外,它还强调了通过蛋白质组学工具发现的有希望的蛋白质特征,以及针对化疗耐药标志的治疗策略,以克服乳腺癌的耐药性。通过利用蛋白质组学技术,我们向化疗耐药乳腺癌更有效和个性化的治疗干预迈进了一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoding the key hallmarks of chemoresistance: A proteomic tale from breast cancer research.

Chemoresistance denotes the intricate, multifactorial molecular mechanisms by which malignant cells subvert the cytotoxicity of chemotherapeutic agents, thereby impeding therapeutic efficacy. This phenomenon is orchestrated through a confluence of processes, which we propose as the major hallmarks of chemoresistance in cancer. Dysregulation of drug transporters, activation of pro-survival pathways, cancer stem cell driven proliferation, DNA damage and repair mechanisms, evasion of apoptosis, autophagy induction, secretion of extracellular vesicles, and metabolic reprogramming represents the major mechanisms of chemoresistance in cancer. Breast cancer is one of the most common and aggressive types of cancer, with significant challenges in treatment due to its heterogeneity. Despite progress in various treatment regimens, chemoresistance continues to be a significant challenge in the effective management of breast cancer. In this context, high-throughput proteomic methodologies, which quantitatively assess proteome-wide alterations and explore post-translational modifications, can provide an unbiased framework for unraveling the molecular intricacies of chemotherapy resistance. This article comprehensively reviews the application of advanced proteomic techniques in elucidating the pathophysiological mechanisms of chemoresistance in breast carcer. Additionally, it highlights promising protein signatures uncovered via proteomic tools, as well as therapeutic strategies targeting chemoresistant hallmarks to overcome drug resistance in breast cancer. By leveraging the mightiness of proteomic technologies, we move closer to efficient, potent and personalized therapeutic interventions for chemoresistant breast cancer.

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