Combining drugs may help fight drug resistance in breast cancer

Cancer Research UK

US researchers have found that combining conventional hormone therapy with an experimental cancer drug helped overcome drug resistance in breast cancer cells in the lab.

“Even more important is that this concept is applicable to overcoming resistance to a whole range of targeted cancer drugs" - Professor Paul Workman 

The research focused on a molecular ‘Sherpa’ that helps cells adapt to stressful environments, known as heat-shock protein 90 (HSP90).

The scientists had previously discovered that HSP90 played a key role in how fungus becomes resistant to antifungal medication.

They then set out to discover whether it was playing a similar role in how oestrogen receptor-positive (ER+) breast cancer became resistant to hormonal therapies such as tamoxifen.

ER+ breast cancer growth is powered by the hormone oestrogen and treated with a therapy that tries to stop or block the effects of the hormone.

But tumours can become resistant to the medication and HSP90 appears to play a key role in helping this resistance develop.

"It's a bit like a game of whack-a-mole, where you knock down estrogen and up pops another growth promoter," says Luke Whitesell, one of the researchers on the study, based at the Whitehead Institute in Massachusetts.

The results, published in Proceedings of the National Academy of Sciences (PNAS), found that even a low dose of a drug that blocks HSP90, called ganetespib, helped prevent drug resistance and stopped the tumour cells from replicating in mice.

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London - who is developing drugs that target HSP90 - said the work was “exciting”.

“It shows that HSP90-inhibiting drugs that are now in the clinic can be used in combination to block the major clinical problem of drug resistance. Also of interest is that the effect is achieved with a low dose of HSP90 inhibitor,” he said.

Workman added: “Even more important is that this concept is applicable to overcoming resistance to a whole range of targeted cancer drugs.”

Trials of ganetespib in combination with hormone therapy are now underway in the US, and the researchers are hoping to see results within the next few years. 

References

  • Whitesell, L., et al. (2014). HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1421323111