Drugs already licensed could be trialled to potentially treat secondary brain cancer, new research finds

Press release issued: 29 November 2023

The largest review of papers for brain cancer that has spread from the lungs has found abnormalities in the brain cancer and for which licensed drugs could be clinically trialled to find out if they could treat the disease. The research led by the University of Bristol and published in Neuro-Oncology Advances also found genetic differences between smokers and non-smokers.

Around 25,000 patients in the UK suffer from cancer that has spread to the brain -known as metastases - most commonly from lung and breast cancer, and causes death in the majority of these patients.

The genetic mutations in primary lung cancers have been widely studied, but less is known about the changes in the cancer once it has spread to the brain. The research team wanted to find out the genetic changes in brain metastasis from non-small cell lung cancer (NSCLC) and whether there are drugs already available that could potentially be offered to these patients.

The researchers carried out a review from 72 papers of genetic mutations in brain metastasis of NSCLC from 2,346 patients’ data on patient demographics, smoking status, genomic data, matched primary NSCLC, and PD-L1, which is a protein found on cancer cells.

The study found the most commonly mutated genes were EGFR, TP53, KRAS, CDKN2A, and STK11. Common missense mutations —mutations that lead to a single amino acid change in the protein coded by the gene— included EGFR L858R and KRAS G12C.

In certain cases the genetic mutations were different in the brain metastasis from the primary lung cancer. There were also differences in the genetic mutations in smokers versus patients who had never smoked. Brain metastases of smokers versus non-smokers had different missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups.

The research team found from the top ten commonly mutated genes which had primary NSCLC data, 37% of the specific mutations assessed were different between primary NSCLC and brain metastases. The researchers suggest Medicines and Healthcare products Regulatory Agency-approved drugs already licensed could potentially be tested to treat the disease in clinical trials.

Read the full University of Bristol news item

'Genomic landscape and actionable mutations of brain metastases derived from non-small cell lung cancer: a systematic review' by Lily J Andrews, Kathreena M Kurian et al. in Neuro-Oncology Advances [open access]