A team of researchers at The Institute of Cancer Research, London, and The Royal Marsden identified several proteins in head and neck cancers which appear responsible for the resistance to drugs called kinase inhibitors.
Treatment of head and neck cancers is particularly challenging because of the hazards associated with delivering radiation to the affected area, and as such, five-year survival rates are lower than in many other cancers.
Head and neck cancers are known to be driven by high levels of the epidermal growth factor receptor (EGFR) and there is a correlation between high EGFR activity and the severity of the disease.
Tyrosine kinase inhibitors (TKIs) are a group of drugs which suppress EGFR. TKI treatment in lung cancer patients results in response rates of up to 74 per cent. However, head and neck cancers are much more resistant, with response rates of only 5-15 per cent.
Researchers at The Institute of Cancer Research (ICR) have identified a resistance-associated protein signature (RAPS) which they believe is responsible for resistance to TKI treatments. Although the research is at a very early stage, if further validated, it could ultimately lead to diagnostic tests using patients’ blood samples to identify individuals who would not benefit from TKI treatment. By understanding the processes which drive aggressive relapse in these cancers, a more personalised therapeutic approach could be offered to patients. The team are currently seeking clinical partners to test for this signature in larger clinical trials.
The research was carried out by the tumour biology and metastasis team at the ICR, and published in the European Journal of Cancer. It was principally funded by Oracle Cancer Trust.
Dr Carol Box, Higher Scientific Officer in Cancer Therapeutics at the ICR, said “Our laboratory tests found that human cancer cells with high levels of the resistance associated protein signature were not only more resistant to TKI treatments, but also much more aggressive.
“A pilot clinical study showed that patients with higher levels of the signature in their blood had shorter survival times. Where TKI treatments initially inhibited tumour growth, the study revealed the tumours often re-grow aggressively once resistance developed.”
Dr Sue Eccles, Team Leader in Tumour Biology and Metastasis at the ICR, said: “It is anticipated that the development of miniaturised, automated assays will improve identification of the molecular mechanisms underlying advanced cancers, and will lead to the development of new targeted drugs.”