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Published on: July 21, 2018
Targeting anaplastic lymphoma kinase in lung cancer
Alice T Shaw1, Benjamin Solomon
1Thoracic Oncology Center, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. ashaw1@partners.org
Abstract:
Several decades of cancer research have revealed a pivotal role for tyrosine kinases as key regulators of signaling pathways, controlling cell growth and differentiation. Deregulation of tyrosine kinase-mediated signaling occurs frequently in cancer and is believed to drive the initiation and progression of disease. Chromosomal rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) occur in a variety of human malignancies including non-small cell lung cancer (NSCLC), anaplastic large cell lymphomas, and inflammatory myofibroblastic tumors. The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066). This review focuses on ALK rearrangements in NSCLC, starting with the discovery of the EML4-ALK fusion oncogene, and culminating in the recent validation of ALK as a therapeutic target in patients with ALK-rearranged NSCLC. Current efforts seek to expand the role of ALK kinase inhibition in lung and other cancers and to address the molecular basis for the development of resistance.
Insights
Anaplastic lymphoma kinase (ALK) rearrangements drive cancer growth, particularly in non-small cell lung cancer (NSCLC). ALK inhibitors show promise as targeted therapies, though resistance mechanisms require further study.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tyrosine kinases regulate cell growth and differentiation; their dysregulation is common in cancer.
- Anaplastic lymphoma kinase (ALK) rearrangements are implicated in various malignancies, including non-small cell lung cancer (NSCLC).
- Aberrant ALK signaling can lead to oncogene addiction and sensitivity to ALK inhibitors.
Purpose of the Study:
- To review the role of ALK rearrangements in NSCLC.
- To discuss the discovery of the EML4-ALK fusion oncogene.
- To highlight ALK as a validated therapeutic target and explore future directions.
Main Methods:
- Literature review focusing on ALK rearrangements in NSCLC.
- Analysis of ALK signaling pathways and their deregulation.
- Examination of ALK inhibitors and resistance mechanisms.
Main Results:
- ALK rearrangements, such as EML4-ALK, are key oncogenic drivers in a subset of NSCLC.
- ALK inhibitors, like crizotinib, demonstrate efficacy in patients with ALK-rearranged NSCLC.
- ALK signaling is a validated therapeutic target.
Conclusions:
- Targeting ALK signaling is a successful strategy for treating specific NSCLC patients.
- Further research is needed to overcome resistance to ALK inhibitors and expand their use to other cancers.
