Johanna A. Joyce, PhD

Cancers develop in a complex microenvironment, in which tumor cells recruit stromal cells from the surrounding tissue and the bone marrow. Bone marrow-derived cells (BMDCs) are among the key stromal cell types in the microenvironment that are proposed to contribute to tumor malignancy; however, the underlying mechanisms are poorly understood. In this project, Dr. Joyce and her colleagues are investigating the roles of BMDC supplied factors, specifically tumor-associated macrophages (TAMs), in promoting malignant progression and blunting therapeutic response. While the tumor microenvironment is known to critically modulate tumor progression, its role in regulating treatment response is poorly understood. The researchers believe that this area of study requires special attention and could have immediate implications for how we treat breast cancer. They recently made the exciting finding that infiltration of BMDCs into tumors increases in laboratory models treated with certain chemotherapeutic drugs, specifically in the macrophage population. Their preclinical trial in a laboratory model of breast cancer shows that targeting macrophage-derived factors, such as cathepsin proteases, in combination with chemotherapy greatly improves therapeutic response. Thus, this research may ultimately lead to therapeutic strategies for enhancing the efficacy of existing FDA approved drugs.

In 2012-2013, Dr. Joyce will continue to investigate the contributions of stromal cells to promoting malignant progression and limiting therapeutic response. Her team will now build upon the solid foundation of exciting results they have generated to date demonstrating the potent roles for TAMs in these processes. They will also investigate whether other stromal cells in the breast tumor microenvironment, in addition to TAMs, modulate the effects of chemotherapy on cell death. The now propose to investigate an array of different breast tumor cell lines, different stromal cell types, and distinct therapeutic agents both in culture and in vivo to investigate how components of the tumor microenvironment may modulate therapeutic response.

Mid-year Progress: Dr. Joyce's results to date strongly support their original hypothesis that TAMs make critical contributions to blunting therapeutic response, in large part by supplying cathepsin proteases. These findings have important implications for their treatment of breast cancer patients, and the ultimate objective of this project is to translate their novel and provocative findings to the clinic, particularly with regard to the logical selection and use of multi-targeted combination therapies. Dr. Joyce's ongoing studies aim to delineate the mechanisms by which TAMs promote chemoresistance and determine the role they play in malignant progression in the context of therapeutic intervention.

Bio:
Dr. Joyce is an Associate Member in the Cancer Biology Program at Memorial Sloan- Kettering Cancer Center (MSKCC) and an Associate Professor in Weill Cornell University Graduate School of Medical Sciences. She received her doctorate in Biology from the University of Cambridge, England in 1999 and completed her postdoctoral training in Dr. Douglas Hanahan's lab at University of California, San Francisco. She joined MSKCC in December 2004 and was named to a Geoffrey Beene Junior Faculty Chair in 2007. Her research interests are to understand the mechanisms by which stromal cells in the tumor microenvironment regulate cancer development, metastasis, and response to therapy.