Drug Combo Shows Promise Treating Aggressive Lung Cancer

Clinical trials are imminent after a recent study showed that a combination of drugs impairs the growth of KRAS lung cancer tumors in mouse models and human samples.

The study was conducted by researchers at the Experimental Oncology Group at the Spanish National Cancer Research Center (CNIO) and published in Nature Medicine.

The paper will document how dasatinib (DDR1 protein inhibitor) and demcizumab (Notch pathway inhibitor antibody) effectively reduces lung adenocarcinomas and improves survival rates in lung cancer treatment.

"Classically, tumors have been studied at advanced stages, but we were interested in studying the initial stages of tumor formation,” said study author Chiara Ambrogio. “We followed this approach to avoid the heterogeneity issue and try to identify new essential mechanisms that sustain tumor development with potential therapeutic uses."

Heterogeneity of lung adenocarcinomas occurs when it reaches advanced stages. The tumor cells evolve over time and learn to adapt to their surroundings to grow and survive while forming sub-populations within the tumor.

For the study, orthotopic mouse models were created by implanting lung tumors from a patient. This method can help determine the efficacy of the drugs when used directly on human tissue samples.

The researchers then analyzed the gene signature of the tumors with large scale gene analysis techniques.

"We discovered that these tumors display high levels of activity of the DDR1 gene, so we decided to validate its inhibition as a potential therapeutic strategy for this type of tumor. One of the advantages of the project is that the 2 drugs employed have already been approved by the regulatory agencies, which will significantly speed-up studies on human patients," Ambrogio said.

The research, which took 5 years, concluded that the combination drugs are able to reduce tumor sizes, prevent further progression, and significantly increase survival rates.

"The next step in this research would be the clinical trials to validate the combination of these drugs as the first therapy directed against these aggressive tumors," Ambrogio said.