Researchers use three-drug combination to treat lung cancer

A study by the Francis Crick Institute and The Institute of Cancer Research, London has tested the combination of a G12C KRAS inhibitor with mTOR and IGF1R inhibitors for the treatment of lung cancer.

The drug acts on a specific mutation in the KRAS gene, which can lead to uncontrollable multiplication of cells, allowing fast growth of cancers.

The mutations are characteristic of 14% of the most common type of lung cancer, lung adenocarcinomas. Most of these cancers lack effective therapies and eight out of ten patients are known to die within five years.

According to researchers, G12C KRAS mutation is responsible for lung cancers of nearly 2,800 individuals in the UK each year.

In clinical trials performed in the US, G12C KRAS inhibitors demonstrate promising anti-tumour activity and few adverse effects. However, additional research is required to determine the duration response before resistance occurs.

The latest study revealed significant shrinkage of lung tumours in mice and human cancer cells treated with the three-drug combination, where the tumours remained small.

However, tumours treated with only the G12C KRAS inhibitor shrank initially but grew within a few weeks.

Study lead researcher Julian Downward said: "It’s likely that tumours will develop resistance to the new drugs, so we need to stay one step ahead. Our results suggest that it would be worth trying this combination in human trials in the coming years, to prevent or at least delay drug resistance."

mTOR, as well as IGF1R inhibitors, have been studied in cancer patients. mTOR inhibitors are available in the market, while IGF1R inhibitors are in the trial stage.

To develop the combination, researchers obtained tumour cells from patients with the G12C KRAS mutation, editing them to block the activity of 16,019 different genes.

Compounds that address the KRAS mutant cancers were then used to treat the cells.

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