Bryan Welm

Breast cancer is not a single disease, but is comprised of distinct molecular subtypes that lead to different clinical outcomes. Over the past 30 years, treatments for breast cancer have evolved with the development of biologics and tailored chemotherapies; however, the majority of breast cancer patients are still vastly over-treated or ineffectively treated. In 2009, there were more than 175,000 new cases and 40,000 deaths from breast cancer in the US, making it the second leading cause of cancer related death in women (American Cancer Society). It has been proposed that modest progress in breast cancer treatment and survival rates may be due to the fact that the disease is very diverse, resulting in inconsistent clinical responses to standard therapies. The development of subtype-specific cancer therapeutics will be critical to overcome this problem.

The presence of specific breast cancer subtypes raises questions about the cellular origin of cancer. Does breast cancer initiate from transformation of stem or progenitor cells that give rise to different tumor subtypes? Or, does the lineage/differentiation capacity of the transformed cell dictate the tumor's subsequent cancer subtype? The relationship between cellular differentiation and transformation has not been thoroughly explored, and it is not known whether specific oncogenic pathways cooperate with intrinsic differentiation programs to establish cancer subtypes.

In order to investigate the molecular processes controlling cancer subtype determination, and facilitate the development of subtype-specific therapeutics, my laboratory is developing new model systems that more appropriately mimic the cellular heterogeneity observed in breast cancer. The main projects in my laboratory are:

Determination of the Cellular Origins of Breast Cancer

We are performing experiments to determine whether specific oncogenic pathways targeted to different mammary epithelial cell populations can affect the cellular composition and pathology of tumors.

Chemical Library Screen to Identify Cancer-Subtype-Specific Therapeutics

The molecular and cellular complexity of breast cancer is not appropriately reproduced with established cell lines. Therefore, we developed a chemical library screen using primary tumor organoids derived from different cancer subtypes. The tumor organoids representing specific subtypes are grown as 3D structures within a laminin-rich extracellular matrix and screened using chemical libraries in order to identify subtype-specific anti-cancer compounds.