Goričar Katja, Dolžan Vita, Lenassi Metka
Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Front Pharmacol. 2021 Apr 30;12:671298. doi: 10.3389/fphar.2021.671298. eCollection 2021.
Biomarkers that can guide cancer therapy based on patients' individual cancer molecular signature can enable a more effective treatment with fewer adverse events. Data on actionable somatic mutations and germline genetic variants, studied by personalized medicine and pharmacogenomics, can be obtained from tumor tissue or blood samples. As tissue biopsy cannot reflect the heterogeneity of the tumor or its temporal changes, liquid biopsy is a promising alternative approach. In recent years, extracellular vesicles (EVs) have emerged as a potential source of biomarkers in liquid biopsy. EVs are a heterogeneous population of membrane bound particles, which are released from all cells and accumulate into body fluids. They contain various proteins, lipids, nucleic acids (miRNA, mRNA, and DNA) and metabolites. In cancer, EV biomolecular composition and concentration are changed. Tumor EVs can promote the remodeling of the tumor microenvironment and pre-metastatic niche formation, and contribute to transfer of oncogenic potential or drug resistance during chemotherapy. This makes them a promising source of minimally invasive biomarkers. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative EV-bound protein and RNA biomarkers were identified. This review is focused on EVs as novel biomarker source for personalized medicine and pharmacogenomics in oncology. As several pharmacogenes and genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment.
能够根据患者个体癌症分子特征指导癌症治疗的生物标志物，可以实现更有效的治疗，且不良事件更少。通过精准医学和药物基因组学研究获得的可操作体细胞突变和种系基因变异数据，可以从肿瘤组织或血液样本中获取。由于组织活检无法反映肿瘤的异质性或其随时间的变化，液体活检是一种很有前景的替代方法。近年来，细胞外囊泡（EVs）已成为液体活检中生物标志物的潜在来源。EVs是一群异质性的膜结合颗粒，由所有细胞释放并积聚在体液中。它们包含各种蛋白质、脂质、核酸（miRNA、mRNA和DNA）和代谢物。在癌症中，EV的生物分子组成和浓度会发生变化。肿瘤EV可以促进肿瘤微环境的重塑和转移前生态位的形成，并在化疗期间促进致癌潜能或耐药性的转移。这使得它们成为微创生物标志物的一个有前景的来源。有限数量的临床研究调查了EVs以监测癌症进展、肿瘤演变或耐药性，并确定了几种假定的与EV结合的蛋白质和RNA生物标志物。这篇综述聚焦于EVs作为肿瘤学中精准医学和药物基因组学的新型生物标志物来源。由于已经在EVs中检测到了几种与靶向治疗、化疗或激素治疗相关的药物基因和基因，它们可能用于微调个性化癌症治疗。
