Final Report Summary - 3DBREASTCANCER (Modeling Breast Cancer in 3D Cell Culture Systems and Mice)
Despite advances in therapeutic treatments, breast cancer remains the second leading cause of cancer related death in women. Mortality rates are largely attributable to typically incurable tumour recurrence at either local or distal sites, which present up to 20+ years following initially successful therapy in a large proportion (30-50%) of patients. It will be important to obtain mechanistic details of tumour therapy, escape and survival of selected cells as well as establishment of recurrent disease to improve treatment options in the clinic. However, due to the problems in tracing and isolating such cell populations from patients, model systems that faithfully re-capitulate the human disease are needed.
We are employing tractable transgenic mouse models of human breast cancer to isolate and study tumour treatment and the switch from tumour dormancy to relapse. Over the past years we have established organotypic 3D cell culture of primary mouse mammary epithelial cells obtained from the above mentioned mice. This system allows monitoring of single cells within a tumour during defined tumour progression stages and gives us a tool to test new hypothesis in a relevant, readily accessible culture setting.
The main aims are directed towards stages during cancer treatment that are elusive to mechanistic analysis in the clinic and include:
• Interfere with the mechanisms important for survival of residual ‘dormant’ cells.
• Identify the molecular properties that allow surviving-residual cells to progress towards recurrence
We are employing tractable transgenic mouse models of human breast cancer to isolate and study tumour treatment and the switch from tumour dormancy to relapse. Over the past years we have established organotypic 3D cell culture of primary mouse mammary epithelial cells obtained from the above mentioned mice. This system allows monitoring of single cells within a tumour during defined tumour progression stages and gives us a tool to test new hypothesis in a relevant, readily accessible culture setting.
The main aims are directed towards stages during cancer treatment that are elusive to mechanistic analysis in the clinic and include:
• Interfere with the mechanisms important for survival of residual ‘dormant’ cells.
• Identify the molecular properties that allow surviving-residual cells to progress towards recurrence