Yuan Pei, Xue Xuemin, Qiu Tian, Ying Jianming
Department of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.
Ther Adv Med Oncol. 2024 Jan 18;16:17588359231221910. doi: 10.1177/17588359231221910. eCollection 2024.
alterations, including exon 14 skipping variants, amplification, overexpression, and fusion, play pivotal roles in primary tumorigenesis and acquired resistance to targeted therapies, especially tyrosine kinase inhibitors. They represent important diagnostic, prognostic, and predictive biomarkers in many solid tumor types. However, the detection of alterations is challenging due to the complexity of alterations and the diversity of platform technologies. Therefore, techniques with high sensitivity, specificity, and reliable molecular detection accuracy are needed to overcome such hindrances and aid in biomarker-guided therapies. The current review emphasizes the role of alterations as oncogenic drivers in a variety of cancers and their involvement in the development of resistance to targeted therapies. Moreover, our review provides an overview of and recommendations on the selection of various cross-platform technologies for the detection of exon 14 skipping variants, amplification, overexpression, and fusion. Furthermore, challenges and hurdles underlying these common detection platforms are discussed.
包括外显子14跳跃变异、扩增、过表达和融合在内的改变在原发性肿瘤发生和对靶向治疗(尤其是酪氨酸激酶抑制剂)的获得性耐药中起关键作用。它们在许多实体瘤类型中代表着重要的诊断、预后和预测生物标志物。然而,由于改变的复杂性和平台技术的多样性,改变的检测具有挑战性。因此,需要具有高灵敏度、特异性和可靠分子检测准确性的技术来克服这些障碍,并助力生物标志物引导的治疗。本综述强调了改变作为多种癌症致癌驱动因素的作用及其在靶向治疗耐药性发展中的参与情况。此外,我们的综述概述了用于检测外显子14跳跃变异、扩增、过表达和融合的各种跨平台技术,并给出了选择建议。此外,还讨论了这些常见检测平台背后的挑战和障碍。