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Review
. 2019 Oct 25;4(5):e000561.
doi: 10.1136/esmoopen-2019-000561. eCollection 2019.

Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review

Anastasia Kougioumtzi  1 , Panagiotis Ntellas  2   3 , Eirini Papadopoulou  4 , George Nasioulas  4 , Eleftherios Kampletsas  2   3 , George Pentheroudakis  2   3
Affiliations
Review

Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review

Anastasia Kougioumtzi et al. ESMO Open. .

Abstract

Background: 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 ALK gene which results in the generation of fusion oncogenes is a common molecular event in NSCLCs. Among ALK fusion transcripts, EML4-ALK 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. Method: 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. Conclusions: Based on the results, the EML4-ALK fusion initially detected in tumour tissue was preserved throughout the course of the disease. Two additional ALK 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.

Keywords: ALK inhibitors; ALK resistance mutations; EML4-ALK fusion; Non-Small-Cell Lung Cancer; molecular profiling.

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Conflict of interest statement

Competing interests: GN and EP are employees of GeneKor Medical SA, Athens, Greece.

Figures

Figure 1
Figure 1
Tumour molecular profiling and treatment strategy. Sequential therapeutic strategy of ALK tyrosine kinase inhibitors (TKI) and chemotherapy over the course of time together with detected molecular findings in patient tissue and plasma. FISH, fluorescent in situ hybridisation; MAF, mutant allele frequency; NGS, next generation sequencing.
See this image and copyright information in PMC

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