Two-drug combination shows potential in ovarian cancer

A pair of experimental drugs slowed tumour growth and blocked resistance mechanisms in ovarian cancer in a new preclinical study.

Researchers found the combination selectively targeted ovarian cancer cells and reduced tumour growth in laboratory and animal models conducted ahead of human trials.

Instead of focusing on individual genetic mutations, the team used a precision medicine strategy based on identifying overactive growth signalling pathways – molecular routes that control how cells grow and divide – in ovarian tumour cells.

The work was carried out by researchers at Weill Cornell Medicine.

Dr Benjamin Hopkins is the study’s senior author and assistant professor of research in physiology and biophysics, and a member of the Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

He said: “Ovarian cancer is challenging to treat because it rarely has common, targetable mutations,” said

“We’re excited by the potential of using this combination in ovarian cancer, and we think this approach will be useful to identify effective treatments against other cancers that don’t contain highly recurrent targetable mutations.”

According to the US National Cancer Institute, nearly 250,000 women are living with ovarian cancer in the US, with around 20,000 new cases each year.

Standard treatment involves surgery to remove the ovaries followed by chemotherapy, but recurrence is common and the five-year survival rate is about 50 per cent.

Ovarian cancer is genetically diverse, with tumours often driven by different mutations. This makes it difficult to treat using therapies that target shared driver mutations – the genetic changes that fuel tumour growth.

Dr Hopkins’ team analysed existing datasets on ovarian tumour samples and found that, despite the genetic variation, many mutations led to overactivity of the MAPK pathway, a signalling route involved in cell growth.

In tests across 32 human cancer cell models, they found that an experimental drug called rigosertib – which targets the MAPK pathway and is being studied in other cancers – was particularly effective against ovarian cancer cells.

However, they also found that blocking the MAPK pathway in ovarian tumour cells partially activated another growth pathway called PI3K/mTOR.

This effect – known as de-repression – can allow cancer cells to survive and grow, contributing to drug resistance.

The team conducted a second round of drug screening using rigosertib combined with various PI3K/mTOR inhibitors, aiming to block both pathways at once.

The results showed that although rigosertib alone outperformed standard platinum-based chemotherapy in preclinical models, combining it with a PI3K/mTOR inhibitor was even more effective.

Dr Hopkins said he hopes these findings will encourage drug developers to explore similar dual-target approaches, including more potent drugs that act like rigosertib.

He said: “We’re also working to identify more of these tumour-specific dependencies in ovarian cancer that could offer further options for second-line therapy—because currently there are no curative second-line therapies available for this cancer.”