THE METASTATIC BREAST CANCER NETWORK SUPPORTS METASTATIC BREAST CANCER RESEARCHERS THROUGH CONTRIBUTIONS MADE TO MBCN
IN MEMORY OF PATIENTS WHOSE LIVES WERE CUT SHORT BY THE DISEASE
Patient-Led Advocate Group Selects Johns Hopkins’ Dr. Andrew Ewald as a 2017 recipient of a $100,000 Metastatic Breast Cancer Research Leadership Award
Since its founding in 2003, members of the Metastatic Breast Cancer Network have worked to educate the public and early stage patients that the major clinical problem that ends lives in breast cancer is metastasis—a complicated process by which cancer cells leave the breast and travel through local tissues and the blood stream to establish themselves as a new tumor in the bone, lung, liver or brain. Once a patient receives a diagnosis of metastatic breast cancer, the focus of treatments is to prolong life for as long as possible while maintaining a good quality of life.
While treatments for certain subtypes of metastatic breast cancer have resulted in improved outcomes for patients, a major barrier to extending life for all subtypes of the disease is the incomplete understanding of the biology of metastasis. As an example, at the recent MBC Alliance meeting in Dallas in January 2016, research participants disagreed as to whether newly detected metastases in patients emerged from latent “seeds” that originated in the primary tumor or whether cancer cells from an existing metastatic site can spread to seed new tumors in another part of the body. This difference is important because it determines the cellular process that needs to be targeted by therapies and affects the design and interpretation of clinical trials.
With support from MBCN in 2015, Dr. Ewald moved his lab’s focus deeper into the study of the metastatic process. His lab developed new models of metastatic tumor formation, entry into blood vessels, and organ-site specific metastasis. The models relied on the use of freshly isolated tissue from primary and metastatic tumors from animal models and from human patients. Dr. Ewald’s research has found that groups of cancer cells seed metastases, not single cells as previously thought. These new findings were published in Proceedings of the National Academy of Sciences. There Dr. Ewald credited MBCN with providing funds that supported the research.
Using 3D culture models of breast cancer, the Ewald lab determined that the cancer cells leading the invasive process express a specific set of “basal epithelial” gene, for example keratin-14 (K14) in both mouse models and diverse human breast cancer tumors. Dr. Ewald’s observation of a consistent program of basal gene expression during invasion across breast cancer subtypes, suggested that the underlying biology of metastasis is similar across many breast cancer patients. Given the tremendous genetic diversity of breast cancer, he suggests that different sets of mutations must somehow provide access to the conserved basal molecular program for metastatic spread. Using MBCN funds provided in 2015, Dr. Ewald’s lab tested invasion and K14 expression in fresh 3D cultures of >60 primary human breast tumors and concluded that when a breast tumor could express K14, it invaded. When a tumor could not express K14, it did not invade.
This preliminary data leads Dr. Ewald to hypothesize that breast cancer cells must activate a “basal” molecular program that enables migration, extracellular matrix interaction and survival in distant organs. However, it remains possible that there are alternate molecular programs that enable the spread of tumors in the body. Each scenario has different diagnostic and therapeutic implications.
MBCN believes it is important to resolve this question—“Is there one path or several to breast cancer metastasis?” Therefore, MBCN has awarded Dr. Ewald a 2017 Research Leadership Award Extension of $100,00. This unrestricted grant will enable him to collaborate with pathologists to distinguish these possibilities in archival samples of patient tumor tissue with known survival and metastasis outcomes. Over the next two years Dr. Ewald will evaluate the prognostic value of K14 as a biomarker in these samples to understand the biology of dissemination, and to test for alternate mechanisms of invasion and dissemination. Finally, Dr. Ewald will use cutting edge gene and protein analysis techniques to identify key molecular features of K14+ metastasis and identify proteins that could be targeted as anti-metastatic therapies.
The Metastatic Breast Cancer Network applauds Dr. Ewald’s leadership in cell biology and metastasis. We look forward to periodic research updates from him. These updates will be shared with our metastatic breast cancer community.
MBCN wants to acknowledge and thank individuals and private corporations that made contributions to MBCN in memory of loved ones and friends whose lives were cut short by metastatic breast cancer. Because of the generosity of family, friends, and work colleagues, this Leadership Award was possible.
“You can think of metastasis as The Amazing Race,” says Ewald. “The cells encounter many different challenges as they attempt to grow and spread, and some cells are better at different events than others, so traveling in a group makes sense.”