Grant: Operating Grant

We propose to determine whether antidepressants may be combined with other anticancer therapies to provide better outcomes for breast cancer patients than are achieved by current therapies. We have discovered that drugs commonly used to treat patients suffering from depression, anxiety or migraines, block the growth of mouse breast tumors. These drugs, which include Prozac, Paxil and Zoloft (sertraline), affect serotonin levels in particular neurons in the brain that control mood. However, serotonin is not restricted to the brain; in fact 95% of the serotonin in our bodies is found in the intestine, heart, platelets and the breast. Studies show that serotonin acts by eliminating milk-secreting cells in the breast after breast-feeding is stopped. Recently it has also been found that both the proteins required to make and respond to serotonin are present in breast tumor cells. We discovered that drugs like Zoloft specifically kill a subset of breast tumour cells, termed cancer stem cells or breast tumour initiating cells, which fuel tumour growth, seed metastases and resist anticancer therapies commonly used to treat breast cancer patients. We also found that Zoloft and chemotherapy work much better together than does either drug alone (a process termed synergy) to shrink breast tumors in a mouse model of breast cancer. Our proposal seeks to learn whether serotonin is required to maintain the breast cancer stem cell subpopulation in human breast tumors and whether drugs that inhibit serotonin function eliminate breast cancer stem cells from tumors thus leading to durable breast cancer remissions. The availability of numerous widely used antidepressants coupled with the inability of current breast cancer therapies to provide durable breast cancer remissions suggests that assessing the feasibility of combining antidepressants with chemotherapies in animal models is a worthwhile endeavour that may lead to new combination therapies for breast cancer patients.