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Pazopanib in advanced soft tissue sarcomas.帕唑帕尼治疗晚期软组织肉瘤。
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Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours.酪氨酸激酶抑制剂对伊马替尼耐药胃肠间质瘤继发 kit 突变的互补作用。
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软组织肉瘤治疗的药物基因组学生物标志物

Pharmacogenomics Biomarkers of Soft Tissue Sarcoma Therapies.

作者信息

Caruso Chiara, Garofalo Cecilia

机构信息

Advanced Translational Research Laboratory, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.

出版信息

Front Oncol. 2020 Apr 15;10:509. doi: 10.3389/fonc.2020.00509. eCollection 2020.

DOI:10.3389/fonc.2020.00509
PMID:32351891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7174622/
Abstract

Soft tissue sarcomas (STS) are heterogeneous rare malignancies comprising ~1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Over the last two decades, the increased knowledge of the new molecular and genomic mechanisms of different STS histotypes allowed for a reclassification of these tumors and consequently to the development of novel chemotherapeutic agents. Generally, surgery, in combination with radiotherapy only in selected cases of localized disease, represents the most common treatment of primary STS, whereas the principal treatment modality for locally advanced or metastatic disease is first-line chemotherapy. The principal treatment for the preponderance of STS patients is usually an anthracycline (epirubicin and doxorubicin) in monotherapy or in combination with other drug novel chemotherapeutic agents. However, survival for treated patients with metastatic disease is poor, and a 2-years survival rate is about 30%. In this scenario, Pharmacogenomics (PGx) biomarkers that can predict drug response play an important role in the improvement of molecular diagnostics in clinical routines and contribute to elucidating the genetic basis for the differences in treatment efficacy and toxicity among STS patients. This review focuses on recent insight in the PGx biomarkers that have been described to modulate responsiveness and toxicity parameters of conventional and new chemotherapeutics drugs in several STS histotypes.

摘要

软组织肉瘤(STS)是一类异质性罕见恶性肿瘤,约占成人所有实体癌的1%,包括70多种具有不同病理和临床发展特征的组织学和分子亚型。在过去二十年中,对不同STS组织类型新的分子和基因组机制的认识不断增加,使得这些肿瘤得以重新分类,并因此开发出了新型化疗药物。一般来说,手术,仅在局部疾病的特定病例中联合放疗,是原发性STS最常见的治疗方法,而局部晚期或转移性疾病的主要治疗方式是一线化疗。大多数STS患者的主要治疗方法通常是使用蒽环类药物(表柔比星和多柔比星)进行单药治疗或与其他新型化疗药物联合使用。然而,转移性疾病患者的生存率较低,两年生存率约为30%。在这种情况下,能够预测药物反应的药物基因组学(PGx)生物标志物在改善临床常规分子诊断中发挥着重要作用,并有助于阐明STS患者治疗疗效和毒性差异的遗传基础。本综述重点关注了最近对PGx生物标志物的见解,这些生物标志物已被描述为可调节几种STS组织类型中传统和新型化疗药物的反应性和毒性参数。