Scientists from Francis Crick Institute found that using immunotherapy alongside a drug that blocks a common gene mutation in lung cancer could be a promising new combination therapy for certain types of lung tumors.
The research is published in Science Advances and was conducted by Julian Downward et al.
Around 1.8 million people die from lung cancer each year, making it the leading cause of cancer death globally. While some people are effectively treated with immunotherapy, this does not work for most patients.
With only a quarter of people surviving more than five years after diagnosis, there is an urgent need to find new treatments or new combinations of existing drugs.
In the study, the team tracked the effects of combining immune checkpoint blockade with KRAS inhibitors in mice.
In tumors where there were already high numbers of active immune cells, so-called “immune hot” tumors, the treatment successfully controlled cancer.
However, in cases where the immune system was not able to mount a strong response, the combination treatment was ineffective.
The researchers are calling for clinical trials to include patients with “immune hot” tumors, to ensure that the potentially effective combination is tested on those most likely to respond.
They say that KRAS inhibitors are very new so there’s still a lot to learn about when they are most effective and which other treatments they can safely be combined with to give patients the best chance of living longer.
This study suggests that combining immune checkpoint blockade with a KRAS inhibitor is likely to work in specific cancers. It is crucial this is factored into the design of future clinical trials.
The team also investigated the impact of the KRAS mutation on the tumor, the environment around the tumor and the immune system.
They found that, in lung cancer, mutated KRAS weakens signals which help activate the immune system while boosting hormone-like molecules which help create an environment that supports the tumor.
The KRAS gene is a member of the RAS family of genes that are implicated in about 20% of all cancers, including melanoma, bowel cancer and pancreatic cancer.
The scientists will continue their work studying the role of this family of genes in cancer, including researching ways it might be possible to stimulate the immune system to eliminate cancer cells that have developed resistance to RAS inhibitors.
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