Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4-ALK-rearranged non-small-cell lung cancer harbored coexisting EGFR mutation

Abstract

Background: The EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLCs). The EML4-ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS.

Case presentation: We report that a case of EML4-ALK-positive NSCLC with EGFR mutation had a response of stable disease to both an EGFR tyrosine kinase inhibitor (EGFR-TKI) and ALK inhibitor.

Conclusions: We described the first clinical report of a patient with EML4-ALK-positive NSCLC with EGFR mutation that had a response of stable disease to both single-agent EGFR-TKI and ALK inhibitor. EML4-ALK translocation may be associated with resistance to EGFR-TKI, and EGFR signaling may contribute to resistance to ALK inhibitor in EML4-ALK-positive NSCLC.

Figure 1

Histology of the primary tumour. (A) and (B) shows a papillary adenocarcinoma (hematoxylin and eosin 200× magnification), (C) a mucin stain shows positive for both signet-ring and papillary morphology (PAS, 400× magnification). (D) immunohistochemical analysis of lung adenocarcinoma specimens with EML4-ALK fusion using a monoclonal anti-TTF-1 antibody (200× magnification).

Figure 2

The sequence of the junction between EML4 exon 20 and ALK exon 20.

Figure 3

Diagnosis of an EML4-ALK-positive non-small cell lung cancer. (A) Immunostaining for ALK protein expression in tumor cells. (B) The results of a break-apart FISH assay of tumor cells from a patient with rearrangement of the gene encoding ALK.