Description: Researchers are investigating a specific protein in cancer that has been found to be involved with both tumor growth and chemoresistance. They hope to observe this protein in the mouse model to develop more effective cancer treatments for triple negative breast cancer.

Start: September 1, 2015
End: August 31, 2018

• Sponsor: National Institutes of Health
• Principal Investigator: Joshua Andersen

Project Description:
Many systems in the human body can adapt to changes in their environment; this adaptation is generally seen as a positive step towards survival. However, in cancer patients, adaption allows cancerous tumors to adapt to chemotherapy, rendering the treatment less effective in eradicating the cancerous tumors. Dr. Anderson and his research team are focusing on a specific protein called 14-3-3ζ that plays a major role in the tumor’s ability to adapt and survive. Typically, this protein assists in autophagy (the body’s digestion of damaged cells). While autophagy is good for a healthy individual, it is harmful to a cancer patient because it allows the tumorous cells to survive. Dr. Andersen is primarily focused on two characteristics of this protein: 1) how exactly this protein responds to stress in its environment (such as chemotherapy), that triggers the adaptation and 2) how to use treatments to target the protein and limit adaptation. Understanding how this protein behaves in stressful circumstances will allow for researchers to discover how to block 14-3-3ζ and its adaptive mechanisms. In order to observe this protein, researchers will use the mouse model.

Intellectual Merit:
In the recent past, research connecting certain proteins to a cell’s level of autophagic flux, or the level at which it controls the digestion of damaged cells, has been conducted. Other data has also revealed positive relationships between a cell’s autophagic flux and its ability to resist chemotherapy treatments. This project merges this data to create a foundation for its main hypothesis: that the stress of low blood supply will negatively rearrange the protein 14-3-3ζ which will in turn interact with other proteins and ultimately lead to chemotherapy resistance in breast cancer. This project is innovative in its approach to understand 14-3-3ζ through the application of the mouse model.

Broader Impact:
Understanding autophagy and the proteins surrounding this emerging means of chemoresistance will lead to the development of more effective chemotherapy treatments. The goal for future chemotherapy will be to target and block 14-3-3ζ in tumors that depend on autophagy for survival. Eventually future chemotherapy treatments will reach larger populations of patients with triple negative breast cancer who may have limited access to other treatments.