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The EML4-ALK oncogene: targeting an essential growth driver in human cancer

Hiroyuki Mano1

  • 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo.

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
|May 15, 2015
PubMed

Insights

Researchers identified the EML4-ALK fusion oncogene in lung adenocarcinoma using functional screening. This discovery led to targeted therapies, like alectinib, demonstrating the success of targeting essential cancer growth drivers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Targeting cancer's essential growth drivers is a key therapeutic strategy.
  • Identifying these drivers in clinical samples requires sensitive screening methods.

Purpose of the Study:

  • To develop a functional screening system for identifying oncogenes in lung adenocarcinoma.
  • To discover novel molecular targets for cancer treatment.

Main Methods:

  • Utilized a retroviral cDNA expression library for functional screening.
  • Employed a focus formation assay on lung adenocarcinoma specimens.
  • Identified the EML4-ALK fusion oncogene resulting from chromosomal inversion.

Main Results:

  • The EML4-ALK fusion oncogene was discovered, linking microtubule-associated protein EML4 with ALK kinase domain.
  • Constitutive dimerization and activation of EML4-ALK were observed.
  • Approved ALK inhibitors (crizotinib, ceritinib, alectinib) show high efficacy in EML4-ALK-positive lung cancer.

Conclusions:

  • The EML4-ALK fusion is a critical oncogenic driver in a subset of lung adenocarcinomas.
  • Targeted therapies inhibiting ALK kinase activity are highly effective, achieving response rates up to 93.5% with alectinib.
  • Targeting essential growth drivers represents a successful strategy for effective cancer treatment.

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