Healthy cells around tumours 'may fuel resistance to cancer drugs'

In collaboration with the Press Association

Tumour cells could be being helped by healthy cells to escape cancer drugs killing them, according to US research.

Healthy cells that make up the 'micro-environment' in and around tumours produce molecules that protect tumour cells from the killing effects of drugs, say experts from the Broad Institute, the Dana-Farber Cancer Institute and Massachusetts General Hospital.

The work, published in the journal Nature, could help to explain why drugs that seem to effectively treat cancer in the lab sometimes only produce partial responses in cancer patients.

Dr John Brognard, from Cancer Research UK's Paterson Institute for Cancer Research in Manchester, said: "We know that tumours can sometimes resist even the most powerful cancer drugs, and understanding what drives this resistance is crucial.

"This fascinating research shows that tumour cells don't just evolve their own ways to combat cancer drugs, but that they might be able to enlist the help of surrounding healthy tissues."

The team grew different types of cancer cells by themselves or together with normal cells to see whether healthy cells could contribute to drug resistance.

They described their results "striking" - drugs that killed cancer cells grown in isolation were rendered ineffective when tumour cells were grown alongside healthy cells.

Dr John Brognard said: "On the surface this is daunting - healthy cells around a tumour could give tumours an innate ability to resist drugs even before the treatment starts. But work like this gives us hope - it shows we can start to unpick these resistance mechanisms early on, even before a new drug is widely used in the clinic."

The researchers went on to focus on melanoma, the most serious form of skin cancer, which is sometimes caused by a fault in a gene called BRAF.

They looked at melanoma cells grown in the lab and found a protein called hepatocyte growth factor (HGF) seemed to help them resist drugs that inhibit BRAF.

The team confirmed the results in melanoma patients. HGF levels in biopsies taken from melanoma patients were low in those who responded well to treatment, and higher in those who responded poorly to treatment.

The research suggests that a combination of BRAF inhibitors alongside HGF-targeted drugs may be effective in fighting melanoma.

Another paper published in the same issue of Nature by Jeffrey Settlemen and colleagues confirms that HGF helps melanoma cells resist drugs that inhibit BRAF.

Copyright Press Association 2012

References

  • Straussman, R. et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature doi:10.1038/nature11183 
  • Wilson, T.R. et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature doi: 10.1038/nature11249