miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC
In: Biochemical and biophysical research communications, Jg. 511 (2019-01-28), Heft 2
Online
unknown
Zugriff:
Lung cancer causes the highest number of cancer-related deaths worldwide. Resistance to therapy is a major clinical issue contributing to the poor prognosis of lung cancer. In recent years, targeted therapy has become a concept where subgroups of non-small cell lung cancer (NSCLC) with genetically altered receptor tyrosine kinases are targeted by tyrosine kinase inhibitors (TKIs). One such subgroup harbors a gene fusion of echinoderm microtubule-associated protein-like 4 (EML4) with anaplastic lymphoma kinase (ALK). Although most NSCLC patients with EML4-ALK fusions initially respond to ALK TKI-therapy they eventually develop resistance. While ALK kinase domain mutations contribute to ALK TKI-refractoriness, they are only present in a fraction of all ALK TKI-resistant tumors. In this study we sought to explore a possible involvement of microRNAs (miRNAs) in conferring resistance to ALK TKIs in ALK TKI-refractory NSCLC cell lines. We subjected our ALK TKI-refractory cancer cells along with parental cancer cells to systematic miRNA expression arrays. Furthermore, ALK TKI-refractory cancer cells were exposed to a synthetic miRNA inhibitory Locked Nucleic Acid (LNA)-library in the presence of ALK TKIs Crizotinib or Lorlatinib. The outcome of the combined approaches uncovered miR-100-5p to confer resistance to Crizotinib and Lorlatinib in EML4-ALK NSCLC cells and to be a potential therapeutic target in drug resistance.
Titel: |
miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC
|
---|---|
Autor/in / Beteiligte Person: | Lewensohn, Rolf ; Stukan, Iga ; Kacal, Merve ; Lai, Yi ; Jatta, Kenbugul ; Ekman, Simon ; Vakifahmetoglu-Norberg, Helin ; Kis, Loránd L. ; Hydbring, Per ; Norberg, Erik ; Kanony, Maraam |
Link: | |
Zeitschrift: | Biochemical and biophysical research communications, Jg. 511 (2019-01-28), Heft 2 |
Veröffentlichung: | 2019 |
Medientyp: | unknown |
ISSN: | 1090-2104 (print) |
Schlagwort: |
|
Sonstiges: |
|