Two-pronged drug attack could treat childhood cancer
A combination of two potential anti-cancer drugs could help block the growth of a particular childhood cancer, according to a study from the Institute of Cancer Research (ICR) in London.
The study looked at two key controls in cancer cells, which can contribute to them becoming resistant to treatment.
By switching off both controls with a combined drug treatment the researchers were able to stop the growth of cancer cells in the lab and in mice.
The researchers focused on rhabdomyosarcoma, a childhood cancer that starts in the muscles.
They found that one of the controls - known as the PI3 kinase pathway - was switched on in 83 per cent of rhabdomyosarcoma samples from patients.
And the other control - known as the MAP kinase pathway - was switched on in 43 per cent of the patient samples where PI3 kinase was also switched on.
Using cells grown in the lab, the researchers then found that if you switched off either one of the two controls the other control became more activated to compensate.
Dr Jane Renshaw, a co-author on the study, said: "We found that while most rhabdomyosarcoma tumours seem to have active PI3K signalling, inhibiting this pathway alone isn't enough to be an effective treatment."
"Cross-talk between the PI3 Kinase and MAP Kinase pathways means that cancer is able to find an alternative route, like traffic finding a way around a road-block."
They reasoned that by blocking both controls they may stop the cells from using either one as an escape route.
To do this, they used two drugs AZD8055 and AZD6244.
The two drugs combined reduced the growth of cancer cells in the lab to a greater extent than either treatment on its own.
And the drug combination reduced levels of a blood tumour marker in mice with rhabdomyosarcoma.
The two drugs are already being tested for treating adult cancers. Dr Renshaw said the next step will be clinical trials for children.
Nell Barrie, Cancer Research UK's Senior Science Communication Manager, said: "Understanding the inner workings of cancer cells is crucial to finding the best ways to tackle the disease.
"This lab research emphasises the importance of targeting each cancer's weak points and combining drugs to develop more effective treatments - which are urgently needed to improve survival for children's cancers like rhabdomyosarcoma."
"Further research and clinical trials will shed light on whether this promising drug combination could help save more lives."
The study was funded by the NIHR Biomedical Research Centre for Cancer at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (ICR), with additional funding from Cancer Research UK, the Chris Lucas Trust and The Royal Marsden Hospital Charitable Fund.
Copyright Press Association 2013
- Renshaw J, et al. (2013). Dual Blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) Pathways Synergistically Inhibits Rhabdomyosarcoma Cell Growth In Vitro and In Vivo, Clinical Cancer Research, 19 (21) 5940-5951. DOI: 10.1158/1078-0432.CCR-13-0850