Study predicts treatment combinations for resistant cancers
Written by Kirsty Oswald, Science Writer
Researchers have created a system to predict how therapies can be combined together to overcome resistance and expand treatment options for hard-to-treat cancers.
The team studied over 2000 two-drug combinations in breast, colorectal and pancreatic cancer cell lines. Combining this information with genetic and multi-omics analysis, they were able to predict effective treatment combinations and identify biomarkers to select patients who may benefit the most.
In total, the team looked at 108,259 combination-cell line pairs. Drugs tested included approved chemotherapies and targeted therapies, as well as drugs in clinical development and investigational compounds.
Overall, the team found that synergy between drugs was rare – it was seen in just 5.2% of the combination-cell line pairs – but it was more likely with targeted agents. Two-thirds of synergistic combinations involved two targeted compounds, while chemotherapeutic agents were less likely to prove synergistic. The researchers also found that for many of these synergistic combinations there were biomarkers which could be used for patient stratification.
To help validate their findings, they tested one of the synergistic combinations in mice using colon cancer cells with specific mutations. This involved an existing targeted therapy used in colon cancer, called irinotecan, in combination with a developmental therapy. In two of the three colon cancer cell lines tested, combination therapy slowed tumour growth and led to smaller tumour size at the end of the study compared with irinotecan treatment alone.
Combining cancer therapies can not only help overcome treatment resistance but could also improve tolerability by reducing doses of individual drugs and may lead to the development of new therapies. Combined therapies are already used in some cancers. But to discover new pairings, it would not be possible to test the sheer number of potential combinations in a clinical trial.
“Resistance to cancer treatments is a huge problem that costs lives, and therefore having other effective therapies available for when the cancer does not respond is vital,” said Dr Mathew Garnett, senior author and group leader at the Wellcome Sanger Institute. “…We hope that this will be used by scientists all over the world to investigate previously unexplored combinations of drugs, leading to new options for those who need it.”
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