Female breast cancer is currently the most diagnosed cancer, with an estimated 2.3 million new cases per year. Breast cancer is known to be initiated by the mutation of specific oncogenes. It has been recently proven, however, that progression of the tumour is dictated by changes in the mechanical microenvironment of the mutated cells. Breast cancer aggressiveness correlates specifically with fibrosis involving the deposition of a collagen matrix by stromal fibroblasts.
When primary breast tumours form stiffer matrices, they also metastasize more. Tumour stage progresses with fibrosis that modulates tumour entry by immune cells, nutrients, gases and anticancer drugs carried by the tumour microvascular network. Pharmaceutical companies are investing billions on the development of personalised treatments for patients who develop recurrent disease after radiation, surgery and/or chemotherapy. To overcome the progressive tumour resistance to anticancer treatments, it would be transformative for the field to understand and control how the tumour fibrotic environment evolves.
The development of tissue is significantly faster in embryonic organisms. The embryonated chicken embryo model has also been used to monitor in vivo the invasive features of human ovarian, thyroid, and skin cancer cells. No one has ever replicated the human cancer fibrotic niche and relevant druggability using this model.
My general goal is to bioengineer an array of tumour fibrotic microenvironments in vivo with varying levels of matrix stiffness and vascularity, and predict mass transport within such environments. My specific goals are: (a) To model 3D tumour micro environments with variable levels of fibrotic progression. (b) To develop an imaging window that incorporates the micro scaffolds, also transparent, oxygen-permeable, biocompatible and implantable in vivo (c) To create an experimental model of cancer fibrotic stiffening in vivo, in the chorioallantoic membrane of an embryonated avian egg. (d) To monitor the fibrotic progression of the tumour micro environments in vivo, in real time. (e) To predict mass transport in the tumour micro environments. (f) To validate the platform, in its ability to reproduce on breast tumours with different fibrotic progression the effect of anticancer drugs, both approved and investigational.
