Ola Larsson

A majority of all women who die as a result of breast cancer belong to a category of breast cancer that expresses the estrogen receptor. This is because most breast cancer patients belong to that category and because resistance to treatment focuses on inhibition of the estrogen receptor, so-called endocrine therapy, continues to occur for at least 20 years after the cancer has been removed. There is currently a lack of effective treatments for breast cancer that have developed resistance to endocrine therapy and it is therefore of utmost importance to find molecular targets that can be used to treat these patients. When genes are expressed, a copy (mRNA) is first made which is used to produce proteins via so-called translation. The estrogen receptor is a key factor for which genes to copy. We have recently discovered that the estrogen receptor also affects which of these mRNAs are translated into proteins. Our preliminary data show that if the estrogen receptor can not affect the translation of mRNA into proteins, it can also not affect cell division, which is one of its key functions in cancer cells. It also seems that if you inhibit the translation that is regulated by the estrogen receptor, you can make cancer cells again sensitive to endocrine treatment. We want to clarify whether translation of mRNA can be used as a target for the treatment of breast cancer with resistance to endocrine therapy. We also want to study, using tissue samples from original breast tumors and their metastases, whether up-regulation of mRNA translation is associated with metastasis. Furthermore, by comparing patients with short and long time to recurrence, we will investigate whether misregulation of mRNA translation is associated with cancer recurrence. Through these studies, we will understand whether translation of mRNA is a target for the treatment of breast cancer that has developed resistance to endocrine therapy.