Non-Small Cell Lung Cancer Therapy Enhanced – Combination Of RNAi With Tyrosine Kinase Inhibitors

iRNA and TKI enhance lung cancer therapy

Combination of iRNA and TKI offer new dimensions to lung cancer therapy. Pic courtesy: http://www.nature.com/scitable/topicpage/gene-expression-14121669

New research published in the journal BMC Medicine, and titled, ‘Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab’, talks about how epidermal growth factor receptor (EGFR) can be blocked using RNAi (RNA interference) along with tyrosine kinase inhibitors (TKI). The combined use can bring about an enhanced TKI effect on non-small cell lung cancer (NSCLC) in terms of cell growth and proliferation. Researchers at Universitair Ziekenhuis Brussel, in Belgium, conducted the research.

Non-small cell lung cancer is the most commonly occurring form of lung cancer. The usual course of treatment for NSCLC is surgery, radiation therapy, chemotherapy etc. About 10% of cases of NSCLC are presented with a gene mutation, in the gene coding for the EGFR and these respond well to TKIs. However, there are a small percentage of patients who do not take to TKIs, or others who respond initially but eventually become TKI resistant. The new study might be an opening to circumvent this issue.

While proteins are manufactured in the cytoplasm, the DNA is within the nucleus. Hence, to make a protein, the cell must copy the DNA sequence for the protein and slap it on a messenger molecule which can move out of the nucleus into the cytoplasm. This messenger molecule is the RNA (mRNA). The RNAi mechanism employed in the research, blocks proper functioning of this intermediary RNA stage. The researchers, Prof De Greve et al, designed a small interfering RNA (siRNA) molecule that would inhibit EGF protein production in cell lines of NSCLC. This siRNA when used in tandem with TKI/monoclonal antibodies, a stronger positive effect in terms of increased apoptosis and decrease in cell growth was observed in comparison to normal treatment alone. The decrease in EGFR mRNA expression was measured using real-time quantitative PCR. Western blot were used for measuring down regulation of EGFR.

These findings extend hope for NSCLC patients who have EGFR mutations. This would also help those patients who do not respond to TKI or have become resistant to it. The research certainly opens up new strategies in lung cancer treatment that needs to be investigated further.

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