Project 1: Breast tumor evolution

Modeling clonal evolution in mouse xenograft models

Cancers develop as a result of somatic evolution. Deciphering the evolutionary dynamics behind this should provide a more accurate understanding of how cancers arise and enable more intelligent approaches toward anti-cancer therapies. However, this area receives almost no experimental attention, and our understanding of clonal evolution in cancers is very rudimentary. To address this deficiency, we have developed a mouse xenograft model of human breast cancers that allows us to follow dynamics of clonal competition in genetically heterogeneous tumors.   

Intratumor heterogeneity and metastasis

Metastatic dissemination of cancer cells is the most prominent cause of death due to breast cancer. Recent work in this field has established that the progression of metastatic invasion from the primary tumor to distant locations (such as bone, lungs, and brain) depends on heterogeneous interactions of cancer cells with each other and with cells composing the microenvironment. We aim to elucidate some of the factors and mechanisms that influence metastatic co-operation between cancer cells and their environment in order to fully understand the metastatic cascade and aid in the development of therapies that address this phenomenon.

Diversity in human breast tumors

Intra-tumor genetic and phenotypic diversity may predict the risk of breast cancer progression and response to treatment. To deepen our understanding of these factors, we have been defining intra-tumor diversity using immuno-FISH and ecological models in breast tumors at different progression stages (i.e., in situ, invasive, metastatic), and before and after chemotherapy or targeted (e.g., antu-Her2) treatment.