Scientists, who tested over 200,000 chemical compounds, have identified 170 candidates that can be potentially used for developing new drug therapies for lung cancer.
The five-year project set out to identify new therapeutic targets for non-small cell lung cancer as well as potential drugs for these targets – a significant step forward towards personalising cancer care, researchers said.
“For the large majority of compounds, we identified a predictive biomarker – a feature that allows the development of ‘precision medicine,’ or individualised treatment for each patient,” said John Minna, from University of Texas in the US.
Therapeutic triads
For the study, published in the journal Cell , the researchers searched for compounds that would kill cancer cells but not harm normal lung cells.
“We began an ambitious project with the goal of identifying ‘therapeutic triads’: chemicals that kill cancer cells, biomarkers that predict who would respond, and the therapeutic targets on which those active chemicals work,” said Minna. Continuing to uncover the mechanism of action for the majority of the 170 chemicals will be a key focus of future research. Follow-up work will also include testing the chemicals on other types of cancer.
Preliminary work shows some of the compounds are likely effective against certain breast and ovarian cancers as well. The researchers have carefully developed and curated a collection of lung cancer cell lines since the 1970s that is now recognised as the world’s largest. The team of scientists began by testing 200,000 chemicals against 12 lung cancer cell lines.
Molecular analysis
“The initial screen gave us 15,000 chemical ‘hits,’ way too many to work with in detail, but with repeat testing we eventually narrowed the number down to 170,” said Bruce Posner, Professor of Biochemistry and Director of the High-Throughput Center at University of Texas. The set of 170 chemical compounds was then tested across 100 lung cancer lines.
At the same time, researchers conducted in-depth molecular analyses of the lung cancer lines, including identification of genome mutations and protein expression. This information, paired with whether or not an individual cancer cell line was sensitive to a particular chemical, allowed the researchers to develop a set of biomarkers - indicators that could be used to determine if a particular cancer will respond to one of the 170 chemical compounds. The final step of the study was determining how the drugs acts on the cancer.
