Laboratory of Clinical Chemistry, University of Ioannina School of Medicine, Ioannina, Greece.
Medical Oncology, University of Ioannina, Ioannina, Greece.
ESMO Open. 2019 Oct 25;4(5):e000561. doi: 10.1136/esmoopen-2019-000561. eCollection 2019.
: Non-small-cell lung cancer (NSCLC) is recognised as a particularly heterogeneous disease, encompassing a wide spectrum of distinct molecular subtypes. With increased understanding of disease biology and mechanisms of progression, treatment of NSCLC has made remarkable progress in the past two decades. Molecular testing is considered the hallmark for the diagnosis and treatment of NSCLC, with liquid biopsies being more and more often applied in the clinical setting during the recent years. Rearrangement of the gene which results in the generation of fusion oncogenes is a common molecular event in NSCLCs. Among fusion transcripts, fusion is frequently observed and can be targeted with ALK tyrosine kinase inhibitors (TKI). However, acquired resistance and disease progression in many cases are inevitable. : Here, we present the case of a patient with NSCLC treated with TKIs, in which molecular profiling of the tumour was performed with different methods of tissue and plasma testing at each disease progression. A review of the literature was further conducted to offer insights into the resistance mechanisms of ALK-rearranged NSCLC. : Based on the results, the fusion initially detected in tumour tissue was preserved throughout the course of the disease. Two additional mutations were later detected in the tissue and plasma and are likely to have caused resistance to the administered TKIs. Continued research into the mechanisms of acquired resistance is required in order to increase the benefit of the patients treated with targeted ALK TKIs.
非小细胞肺癌（NSCLC）被认为是一种特别具有异质性的疾病，包含广泛的不同分子亚型。随着对疾病生物学和进展机制的认识不断提高，过去二十年中 NSCLC 的治疗取得了显著进展。分子检测被认为是 NSCLC 诊断和治疗的标志，近年来液体活检在临床实践中越来越多地得到应用。 基因重排导致融合癌基因的产生是 NSCLCs 中的常见分子事件。在融合转录本中，融合经常被观察到，可以用 ALK 酪氨酸激酶抑制剂（TKI）进行靶向治疗。然而，在许多情况下，获得性耐药和疾病进展是不可避免的。
在这里，我们介绍了一位接受 TKI 治疗的 NSCLC 患者的病例，在每次疾病进展时，都使用不同的组织和血浆检测方法对肿瘤进行了分子谱分析。进一步对文献进行了回顾，以深入了解 ALK 重排 NSCLC 的耐药机制。
根据结果，最初在肿瘤组织中检测到的融合在整个疾病过程中都保留下来。后来在组织和血浆中又检测到了另外两个 突变，这很可能导致了对给予的 TKI 的耐药。需要继续研究获得性耐药的机制，以提高接受靶向 ALK TKI 治疗的患者的获益。
