Johanna A. Joyce, PhD
Geoffrey Beene Junior Faculty Chair
Associate Member, Cancer Biology Program
Memorial Sloan-Kettering Cancer Center
Associate Professor, Weill Cornell Graduate School of Medical Sciences
New York, New York
2013-2014 BCRF Project:
(The ANN INC. Award)
Cancers develop in a complex microenvironment, in which tumor cells “hijack” non-cancerous stromal cells from the surrounding tissue and the bone marrow. Tumor-associated macrophages (TAMs) are among the key stromal cell types in the microenvironment that are proposed to contribute to tumor malignancy in this way, however the underlying mechanisms are still being elucidated.
In this project, Dr. Joyce is investigating the roles of TAM-supplied factors in promoting malignant progression and blunting therapeutic response in breast cancer. She believes that this area of study requires special attention and could have immediate implications for how to treat patients with breast cancer. Dr. Joyce’s group recently found that TAM accumulation in breast tumors increases in mice and patients treated with certain chemotherapeutic drugs. They showed that TAMs surprisingly protected tumor cells against chemotherapy-induced death. They found that this protection was mediated in large part via a specific set of enzymes, members of the cathepsin protease family. Dr. Joyce and colleagues have further extended these results to the analysis of human samples and have established an experimental system to investigate the interaction between TAMs and breast cancer cells isolated from patients.
Together, their results to date strongly support their original hypothesis that bone marrow derived cells make critical contributions to blunting therapeutic response, in large part by supplying cathepsin proteases. These findings have important implications for the treatment of breast cancer patients, and the ultimate objective of this project is to translate the research team’s novel and provocative findings to the clinic, particularly with regard to the logical selection and use of multi-targeted combination therapies. In the continuation of this project, Dr. Joyce is expanding on these findings by investigating how TAMs modulate signaling and transcriptional pathways in tumor cells. This will allow the investigators to understand how TAMs can influence whether or not a tumor cell dies in response to chemotherapeutic treatment. Thus, this research may ultimately lead to therapeutic strategies for enhancing the efficacy of existing FDA-approved drugs.
Dr. Joyce’s team is expanding on their earlier findings on tumor-associated macrophages (TAMs) by investigating the molecular mechanisms of response to chemotherapeutic agents, and how these responses are modulated by TAMs. Moreover, they have recently expanded their investigation into the role of adipocyte lineage cells in chemotherapeutic response in order to optimize treatment for obese breast cancer patients. Thus, this research may ultimately lead to therapeutic strategies for enhancing the efficacy of existing FDA-approved drugs.
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.