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Double-pronged attack could treat common children's cancer
Date:11/1/2013

habdomyosarcoma samples from patients, and that 43% of these also showed activation of the MAP Kinase pathway. In experiments on rhabdomyosarcoma cells to block either pathway alone, they saw compensatory signalling through the alternative pathway, suggesting that inhibiting both pathways is an essential approach to treatment, irrespective of whether MAP kinase signalling was initially activated.

The researchers tested rhabdomyosarcomas with drugs known to be effective against the PI3 Kinase and MAP Kinase pathways. When they tried the drugs AZD8055 and AZD6244 separately they saw reduced cell growth and a decrease in levels of markers showing the activity of the signalling pathways. However, compensatory activity was clearly evident.

But when they combined the two drugs they found a synergistic effect, with cell growth reduced to a greater extent than with either treatment alone. They saw similar synergistic results when AZD8055 and AZD6244 were used together in mice with rhabdomyosarcoma tumours, with tumour marker levels reduced to less than 30% of those in controls.

Co-author Dr Janet Shipley, Team Leader in Sarcoma Molecular Pathology at The Institute of Cancer Research, said:

"Rhabdomyosarcoma is the main type of sarcoma to affect children and little improvement has been made recently using conventional treatments like chemotherapy and radiotherapy - survival rates for some patients with this disease remain bleak. More effective targeted treatment is desperately needed. Our study shows that treating with one or other of these two drugs is not a good strategy but that combining them is a very promising option."

Co-author Dr Jane Renshaw, Senior Scientific Officer at The Institute of Cancer Research, 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 pa
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Contact: Lauren King
lauren.king@icr.ac.uk
020-715-35380
Institute of Cancer Research
Source:Eurekalert

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