By screening already approved drugs, the team led by Postdoctoral Researcher Guillaume Jacquemet and Academy Professor Johanna Ivaska has discovered that calcium channel blockers can efficiently stop cancer cell invasion in vitro.
‘Calcium channel blockers target Myosin-10 protein which blocks the movement of sticky fingers rendering them inactive and blocking cancer cell movement.’
Calcium channel blockers are currently used to treat hypertension, also known as high blood pressure, but their potential use in blocking cancer cell metastases has not been previously reported.
Developing new drugs, however, is a very lengthy and expensive process and many promising drugs fail clinical trials because of unanticipated toxicity and side effects. Thus, finding new targets for drugs already in use to treat other diseases, in other words drug repurposing, is an emerging area in developing anti-cancer therapies.
The team has identified that aggressively spreading cancer cells express a protein called Myosin-10 which drives cancer cell motility. Cell motility is involved at every stage of tumorigenesis and contributes to primary tumour growth, cancer cell dissemination and metastasis formation.
Myosin-10 expressing cancers have a large number of structures called filopodia. They are sticky finger-like structures the cancer cells extend to sense their environment and to navigate - imagine a walking blind spider, explains Dr Jacquemet.
The team found that calcium channel blockers target specifically these sticky fingers rendering them inactive, thus efficiently blocking cancer cell movement. This suggest that they might be effective drugs against cancer metastasis. However, at this stage much more work is required to assess if these drugs would be efficient against cancer progression.
"Identification of anti-hypertension drugs as potential therapeutics against breast and pancreatic cancer metastasis was a big surprise. The targets of these drugs were not known to be present in cancer cells and therefore no one had considered the possibility that these drugs might be effective against aggressive cancer types", said Professor Ivaska.
- Guillaume Jacquemet et al.,L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling, Nature Communications (2016),