Topic Overview:

Zhang is investigating the activated signaling pathways within the tumorigenic stem cell population, its interaction with other tumor cells, and the microenvironment, using a p53 null mouse model of mammary cancer and xenograft models of human breast cancer. She has demonstrated that tumor-initiating cells (TICs) isolated from the p53 null mouse mammary tumors repair DNA damage following in vivo ionizing radiation more efficiently than the bulk of the tumor cells. This effect is accompanied by increased Akt signaling, as well as the direct activation of the canonical Wnt/β-catenin signaling pathway, specifically within the TIC subpopulation. Pharmacological inhibition of the Akt pathway in syngeneic mice-bearing tumors has shown to inhibit canonical Wnt signaling as well as repair of DNA damage selectively in TICs, sensitizing them to ionizing radiation treatment.

Intratumoral heterogeneity reflects the cellular complexity and dynamics within a tumor and is a hallmark of most cancers, including breast cancer. Such clonal heterogeneity is thought to contribute to radio- and chemoresistance since many treatments may only target certain subpopulations of the cells within the tumor. Therefore, targeting the TICs, as well as the functional interaction between various cell types, may help improve the treatment response.

Currently, Zhang is in the process of characterizing the functional interactions between the various subpopulations of cells within a tumor, which may help in the development of effective cancer treatments.