Breast cancer is commonly divided into four subtypes based on the presence/absence of three distinct receptors: Luminal A, luminal B, HER2, and triple negative/basal-like. Triple negative breast cancer (TNBC) affects approximately 15% of breast cancer patients and has a poorer prognosis than the other subtypes. A major challenge associated with breast cancer in general and TNBC in particular is the heterogeneity of the disease, both between patients and within individual tumors. This has hampered efforts to develop effective therapies. As pointed out by others the ability to describe tumors at the resolution of single cells will enhance our ability to determine the best treatment options and to anticipate disease outcome. The proposed multidisciplinary research program seeks to develop and apply a technology that simultaneously assesses the intracellular signaling activity of multiple enzymes at the single cell level in TNBC. We'll compare and contrast the influence of 2D and 3D cell culture conditions as well as antagonists and agonists on signaling activity. In addition, we'll evaluate the presence of subpopulations exhibiting unique signaling behavior. The ability to define heterogeneous aberrant signaling behavior at the single cell level on a patient-by-patient basis could address what is widely viewed as the single most pressing need in TNBC: the absence of guidelines to manage patients with triple-negative disease.

Public Health Relevance

Triple negative breast cancer (TNBC) affects approximately 15% of breast cancer patients and has a poorer prognosis than the other subtypes. A major challenge associated with breast cancer in general and TNBC in particular is the heterogeneity of the disease, both between patients and within individual tumors. We seek to develop a new technology to detect the aberrant biochemistry at the single cell level in tissue from TNBC patients, which could establish the basis for designing unique drug cocktails in a patient-personalized fashion.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA203032-04
Application #
9628653
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Knowlton, John R
Project Start
2016-02-02
Project End
2021-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Pharmacy
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Vickerman, Brianna M; Anttila, Matthew M; Petersen, Brae V et al. (2018) Design and Application of Sensors for Chemical Cytometry. ACS Chem Biol 13:1741-1751
Mainz, Emilie R; Wang, Qunzhao; Lawrence, David S et al. (2016) An Integrated Chemical Cytometry Method: Shining a Light on Akt Activity in Single Cells. Angew Chem Int Ed Engl 55:13095-13098