Cancer cells may no longer be able to dodge drug therapies thanks to a new method, suggests new research.
When a road shuts down because of an accident or construction work, drivers find another route.
Likewise, when a targeted therapy blocks a pathway that enables tumours to grow, the cells usually manage to get around that obstacle – with the result being drug resistance.
But their days may be numbered, as researchers have now found a way to map those alternate routes by studying individual cancer cells, suggesting approaches for developing more effective combination therapies.
Professor Jim Heath, of the NanoSystems Biology Cancer Centre at the California Institute of Technology, said: “Because technology now allows us to see the alternate pathways that cancer cells use to drive growth, it will enable us to identify ways to cut off multiple roads at the same time.”
For the study, published in the journal Cancer Cell, the researchers looked at glioblastoma, the most deadly form of brain cancer.
Although therapies based on genetic alterations in these tumours have been developed, their benefit is usually short lived.
Combination therapies, which target multiple alterations at the same time, may offer a better way to fight this disease, the scientists say.
Professor Paul Mischel, of the Ludwig Institute for Cancer Research at the University of California, said: “Figuring out why resistance to targeted therapies develops has been the focus of our research for a long time.
“In this study, we looked at a drug that should work and found out why it doesn’t.”
The technology the team used is called single cell phosphoproteomics. The tool allowed the team to peer into the inner workings of individual cancer cells and see their signalling.
Using patient tissues obtained directly from operating rooms, the researchers found that the cells began to adapt to and resist therapies that target the growth pathway – called mTOR – in as little as 48 hours.
Analysis showed that these cells were remapping their routes and finding ways to evade the drug’s effect long before any changes could be detected at the clinical level.
The investigators say that this approach could eventually be used to find better combination therapies for glioblastoma, but obstacles remain.
Prof Heath said: “Although the technology used to analyse the cells is relatively simple and inexpensive – just glass and plastic – trials will be difficult to design.
“For this type of personalised treatment, we won’t know what drugs to give patients until after their tumours are analysed. Every trial will essentially have a sample size of one.”
Prof Mischel said there are additional challenges in developing drugs for glioblastoma because they must be able to cross the blood-brain barrier.
The method of studying single cells could also be used to develop personalised treatment for other types of cancer as well, the scientists conclude.
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