Study highlights which rare ovarian cancer patients benefit most from targeted drug therapy

Low-grade serous ovarian carcinoma (LGSOC) is an uncommon form of ovarian cancer that tends to occur in younger women and does not usually respond well to standard chemotherapy. 

A clinical trial between the UK and US found that trametinib significantly delayed cancer progression compared to standard treatments.

In this follow-up study, led by researchers at the Institute of Genetics and Cancer and the MD Anderson Cancer Centre in Texas, tumour samples from 170 of the trial participants were analysed to explore why some patients benefited more from trametinib. 

Researchers examined the tumours’ genetic makeup using genetic sequencing and also measured the activity of the MAPK pathway - a chain of proteins that communicates signals from a receptor on the cell surface to the DNA in the cell’s nucleus - using a protein marker called pERK. 

Patients treated with trametinib whose tumours showed high pERK levels experienced a longer period of therapy benefit compared to those with tumours that had low pERK levels. 

Tumours carrying mutations in key MAPK pathway genes (KRAS, BRAF, or NRAS) were more likely to shrink in response to trametinib treatment.

Overall, the findings suggest that high pERK expression and the presence of specific MAPK pathway mutations may help identify LGSOC patients most likely to benefit from trametinib.