Concomitance of EGFR mutations and ALK rearrangement in patients with Lung Cancer

Targeted therapy is the most popular treatment used against lung cancer. It is usually associated with the mutual status of several genes, mainly epithelial growth factor receptor (EGFR), Kirsten rat sarcoma viral (K-Ras) and anaplastic lymphoma kinase (ALK) fusion gene. The EGFR mutations and EML4 (Echinoderm Microtubule Associated Protein Like 4) -ALK fusion are considered mutually exclusive in non-small cell lung cancers (NSCLCs), but different studies have reported cases harboring a concomitance of EGFR mutations and ALK rearrangement affecting the sensibility to treatments in some cases. Herein, we reviewed the cases reporting this co-alteration since its first discovery in 2008 and describing the patients' response to therapy. We found that a combination of crizotinib and EGFR-TKIs is preferred to overcome the resistance to TKIs by inhibiting both EGFR and ALK pathways. This review demonstrated the necessity of genotyping both EGFR and ALK alterations to guide the clinicians to a personalized therapy for each patient.