EML4‑ALK fusion gene in non‑small cell lung cancer (Review)

Abstract

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate that is a threat to human health. With the development of molecular targeted research, breakthroughs have been made on the molecular mechanism of lung cancer. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is one of the most important pathogenic driver genes of NSCLC discovered thus far. Four generations of targeted drugs for EML4-ALK have been developed, with patients benefiting significantly from these drugs. Therefore, EML4-ALK has become a research hotspot in NSCLC. The aim of the present study is to introduce the current research progress of EML4-ALK and its association with NSCLC. Contents 1. Introduction 2. EML4-ALK fusion gene 3. Clinical features of EML4-ALK in NSCLC 4. EML4-ALK detection method 5.

Postoperative pathological complete response in a patient with PD‑L1‑negative stage IIIB lung squamous cell carcinoma following neoadjuvant tislelizumab treatment combined with chemotherapy: A case report and literature review

“…Squamous lung cancer represents the most prevalent subtype of NSCLC. The occurrence rate of common driver gene mutations, such as EGFR mutations and ALK gene rearrangements, in lung squamous cell carcinoma is generally low, ~2.7 and 1.5-2.5%, respectively (23)(24)(25). Therefore, only a small proportion of patients with squamous cell carcinoma have the opportunity to receive treatment with EGFR-tyrosine kinase inhibitors or ALK inhibitors.…”

ALK‑positive locally advanced lung cancer in a patient who achieved long‑term complete response with crizotinib: A case report

“…The second issue is that the effect of the EML4-ALK variant on ALK inhibitor selection has not been clarified. It has been established that ~20 echinoderm microtubule-associated protein like 4 (EML4)-ALK fusion subtypes exist (24). Fusion variants are classified according to their breakpoints (24).…”

“…It has been established that ~20 echinoderm microtubule-associated protein like 4 (EML4)-ALK fusion subtypes exist (24). Fusion variants are classified according to their breakpoints (24). The most common EML4-ALK variants are v1, v2 and v3a/b; the two EML4-ALK variants that together account for up to 70-80% of all EML4-ALK variants are v1 and v3a/b (25).…”

Kinase inhibitor macrocycles: a perspective on limiting conformational flexibility when targeting the kinome with small molecules

“…59,60 ALK-fusions are oncogenic drivers in diffuse large-B-cell lymphoma (DLBCL), 61 inflammatory myofibroblastic tumors (IMTs), 62 and in 3-7% of non-smallcell lung carcinomas (NSCLC). [63][64][65][66][67][68] Crizotinib (PF-02341066), a MET, ALK, and ROS1 kinase inhibitor received FDA approval in 2011 for the treatment of ALK-positive NSCLC. 69,70 Unfortunately patients receiving crizotinib eventually developed resistance from on-target ALK mutations and CNS issues.…”