Precision medicine progress sees US researchers a step closer to a new combination treatment for chemo-resistant ovarian cancers
Researchers from Weill Cornell Medicine in the US recently published findings thanks to a new precision medicine approach for ovarian cancer.
A two-pronged approach, in preclinical models the combination treatment:
- reduced tumour growth more than standard platinum-based chemotherapy,
- selectively targeted ovarian cancer cells and not healthy cells, reducing side effects compared to current treatments,
- were effective in chemo-resistant samples from multiple types of ovarian cancer.
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Often precision medicine relies on one mutation or target being identified, then a drug or therapy being found to stop it specifically. However, ovarian cancers are considered ‘genetically diverse’ and can result from multiple mutations and changes in various genes, presenting a challenge for selective targeting.
By automating the testing of various drugs on ovarian cancer samples and analysing large cancer protein datasets, the team found two pathways commonly altered across different ovarian cancer cases. Targeting these pathways could stop or slow the progression of a range of ovarian cancer-driving mutations.
In seven cell lines that represented various genetic backgrounds and ovarian cancer subtypes, researchers screened drug compounds to see which could slow activities of one of these pathways, called the MAPK pathway, therefore slowing activation of cancer proteins and prohibiting tumour growth. They identified rigosertib, a drug being tested in other cancers, effectively supressed cancer-causing processes.
Additionally, rigosertib had another benefit; it partially stopped processes of another pathway, P13K/mTOR — suggesting rigosertib could help overcome ovarian cancer drug resistance. Researchers then tested rigosertib in pre-clinical models combined with a P13K/mTOR inhibitor called taselisib, hoping to boost the treatment’s effectiveness against chemo-resistant ovarian cancer.
Results showed that alone rigosertib was more effective than standard platinum-based chemotherapy and results only got better when the combination of rigosertib and taselisib was used.
Next the team hope to test the combination in metastatic ovarian cancer models. They’ll also test different formulas, substituting different P13K/mTOR inhibitor therapies to see which works best for different ovarian cancer subtypes.
Ovarian cancer can recur following initial treatment and become resistant to available treatments, so new second line treatment advances, such as this combination therapy, represent crucial progress.
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