U.S. flag An official website of the United States government

On Oct. 1, 2024, the FDA began implementing a reorganization impacting many parts of the agency. We are in the process of updating FDA.gov content to reflect these changes.

U.S. Food and Drug Administration
  1. Home
  2. Science & Research
  3. Science and Research Special Topics
  4. Advancing Regulatory Science
  5. Identification and Validation of Biomarkers for Breast Cancer Resistance Protein
  1. Advancing Regulatory Science

Identification and Validation of Biomarkers for Breast Cancer Resistance Protein

CERSI Collaborators: University of California at San Francisco (UCSF): Kathy Giacomini, PhD; Mina Azimi, PhD; Sook Wah Yee, PhD; Kelsey Trumbach, MPH

FDA Collaborators: Center for Drug Evaluation and Research: Shiew Mei Huang, PhD; Lei Zhang, PhD; Qi Liu, PhD; Xinning Yang, PhD

Project Start Date: March 1,2020

Regulatory Science Challenge

Drug transporters are found in all body tissues and help move essential nutrients and metabolites into and out of cells. They also help the body absorb, distribute, and remove drugs. Many factors, such as taking different medications together, can affect the activity of these transporters, which in turn may affect drug levels in the body and in various tissues. Too high drug levels could cause drug toxicities, and too low drug levels would not be effective. As a result, clinical research studies often examine possible drug-drug interactions with transporters in cellular assays. Unfortunately, cellular studies can produce incorrect results about drug-drug interactions.

An alternate way to study transporter activity is to measure how changes in the activity or levels of transporters can affect biomarkers. Transporter biomarkers are endogenous molecules present in our blood that reflect the biological activity of transporters. When the activity is low, the biomarker levels will be elevated and when the transporter activity is high, the biomarker levels are reduced. However, the transporter called Breast Cancer Resistance Protein (BCRP) does not yet have a defined set of biomarkers to accurately measure its activity. BCRP is an important transporter that can be found in many tissues (such as the intestine) and is involved in many biological processes such as the oral absorption of many drugs.

Project Description and Goals

Existing research on mice and genetic studies in humans have already identified potential biomarkers for BCRP. The overall goal of this study is to validate these BCRP biomarkers in humans using two approaches. The first approach will involve use of cellular assays to confirm the BCRP biomarker and determine if the biomarkers also interact with other transporters. The second approach will involve conducting a clinical study with healthy volunteers who will take two drugs: rosuvastatin (which uses the BCRP transporter) and eltrombopag (which blocks the BCRP transporter). Biomarkers and drug levels will then be measured in blood samples to determine whether BCRP activity is reduced by eltrombopag. If reduced, rosuvastatin levels and levels of the biomarkers will be increased.

Back to Top