Results from a phase I drug trial show promise for the development of a treatment that may halt the progression of a number of advanced cancers through the inhibition of signalling processes along the Notch signalling pathway.
Research suggests that the Notch signalling pathway plays a role in helping cancer cells to grow, divide and spread around the body; it is also involved in angiogenesis, the process by which tumours grow new blood vessels, and it may contribute to tumours becoming resistant to chemotherapy.
In a study of 103 patients, a drug called LY3039478 showed signs of successfully stopping the progression of cancer and shrinking tumors in patients with a broad range of cancers that were advanced or had begun to metastasise.
This was a proof of concept trial that has shown that LY3039478 is successful in inhibiting unregulated Notch signalling, resulting in encouraging signs of preliminary clinical activity in several advanced and metastatic cancers. One of the interesting results with implications for some patients is that the drug was active against rare cancers such as adenoid cystic carcinoma.
Four Notch receptors within the Notch signalling pathway are responsible for carrying messages across the membranes of cells – including cancer cells. Suppressing these signalling processes prevents the growth or spread of the cancer.
Notch was evaluated as a target for anti-cancer drugs several years ago, with promising results in lymphoma and rare cancers.
Image credit: Wellcome Collection