A study by The Institute of Cancer Research (ICR) in the UK has found that crizotinib could be a potential targeted therapy for breast cancer.
Manufactured by Pfizer, crizotinib is designed to inhibit cell surface receptor ROS1.
The drug is currently approved for non-small cell lung cancer treatment and was observed to destroy ‘lobular’ breast cancer cells with a specific genetic defect in E-cadherin protein.
E-cadherin defects are found in more than 13% of breast cancer patients, and in up to 90% of all lobular breast cancers.
Even though about 7,150 women in the UK are diagnosed with breast tumours with E-cadherin defects, there is currently a lack of drugs selectively targeting these defects.
Researchers tested 80 small-molecule inhibitors to see if any of these drugs caused cancer cells with a defective E-cadherin gene to die.
Crizotinib exhibited significant synthetic lethality, an approach that targets weaknesses in tumour cells.
Based on the results, the team concluded that blocking ROS1 leads to the death of tumour cells that did not have ‘fully functioning’ E-cadherin proteins.
To further validate the findings, the ICR and The Royal Marsden NHS Foundation Trust are initiating a Phase II clinical trial in alliance with Pfizer to assess crizotinib’s efficacy in subjects suffering from advanced lobular breast cancer.
Researchers hope that the drug can provide a targeted treatment for breast cancer, with potential applications in other types of tumours with E-cadherin defects such as stomach cancers.
Breast Cancer Now chief executive Baroness Delyth Morgan said: “This is an extremely exciting discovery that, if proven as effective in trials, could enable the breakthrough re-purposing of a lung cancer drug to provide the first targeted therapy for thousands of women with lobular breast cancer.
“While there is still some way to go, this promising approach demonstrates the real potential of collaboration between academia and industry to speed up the discovery of new cancer treatments and we very much look forward to following the progress of this trial.”