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Updated: Aug 5, 2025
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Published on: July 5, 2019
Molecular Anatomy of the EML4-ALK Fusion Protein for the Development of Novel Anticancer Drugs
So Yeong Cheon1,2, Sunghark Kwon1
1Department of Biotechnology, Konkuk University, Chungju 27478, Republic of Korea.
Abstract:
The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene in non-small-cell lung cancer (NSCLC) was first identified in 2007. As the EML4-ALK fusion protein promotes carcinogenesis in lung cells, much attention has been paid to it, leading to the development of therapies for patients with NSCLC. These therapies include ALK tyrosine kinase inhibitors and heat shock protein 90 inhibitors. However, detailed information on the entire structure and function of the EML4-ALK protein remains deficient, and there are many obstacles to overcome in the development of novel anticancer agents. In this review, we describe the respective partial structures of EML4 and ALK that are known to date. In addition to their structures, noteworthy structural features and launched inhibitors of the EML4-ALK protein are summarized. Furthermore, based on the structural features and inhibitor-binding modes, we discuss strategies for the development of novel inhibitors targeting the EML4-ALK protein.
Insights
The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion protein drives lung cancer. This review details EML4-ALK structures and inhibitors, guiding novel anticancer agent development.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The EML4-ALK fusion gene, identified in 2007, is a key driver in non-small-cell lung cancer (NSCLC).
- The EML4-ALK fusion protein promotes lung cell carcinogenesis, necessitating targeted therapies.
- Existing therapies include ALK tyrosine kinase inhibitors and heat shock protein 90 inhibitors, but knowledge gaps persist.
Purpose of the Study:
- To review known partial structures of EML4 and ALK proteins.
- To summarize noteworthy structural features of the EML4-ALK fusion protein.
- To discuss strategies for developing novel EML4-ALK inhibitors based on structural insights.
Main Methods:
- Literature review of EML4-ALK structures.
- Analysis of known structural features and inhibitor-binding modes.
- Synthesis of information to propose future drug development strategies.
Main Results:
- Partial structures of EML4 and ALK are partially elucidated.
- Key structural features influencing EML4-ALK function are identified.
- Launched inhibitors targeting EML4-ALK are summarized.
Conclusions:
- Detailed understanding of EML4-ALK structure and function remains incomplete.
- Structural insights and inhibitor-binding modes are crucial for novel anticancer agent development.
- Further research into EML4-ALK structure is essential for overcoming therapeutic obstacles.
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