Asha Mohapatra
Pronouns: she/her
Research Mentor(s): Alnawaz Rehemtulla
Research Mentor School/College/Department: Radiation Oncology / Medicine
Program:
Authors: Asha Mohapatra, Alnawaz Rehemtulla, Sahezeel Awadia
Session: Session 1: 9:00 am – 9:50 am
Poster: 11
Abstract
Hormone receptor-positive breast cancer is commonly treated using drugs that inhibit the activity of cyclin-dependent kinases 4 and 6 (CDK 4/6). CDK 4/6 are required for entry of cells into the cell cycle. The kinase activity of these enzymes require their interaction with Cyclin D. Upon binding to Cyclin D, CDK 4/6 phosphorylate the retinoblastoma (Rb) protein. The phosphorylated Rb protein dissociates from the E2F transcription factor, allowing it to transcribe a number of proteins required in the S-phase of the cell cycle, including cyclin E and Emi. Since CDK 4/6 activity is essential for transition of cells from G1 to S phase, inhibition of their kinase activity serves as an effective treatment to block the growth of breast cancer tumors, which is now approved by the FDA. However, women treated with these kinase inhibitors often become resistant to these drugs leading to tumor recurrence, indicating the presence of alternate pathways for entry into the cell cycle. Studies from our laboratory have demonstrated that the protein FADD functions as an alternate pathway that allows the cells to proceed from the G1 to S phase. To promote cell cycle entry, FADD needs to be phosphorylated by casein kinase 1a. Therefore, we propose that inhibition of CK1a provides an opportunity to prevent CDK 4/6 inhibitor resistant tumors to re-enter the cell cycle, and hence to manage breast cancer patients who develop CDK4/6 resistant breast cancer. My research this semester involved the evaluation of a CK1a targeted drug as a way to prevent the re-entry of cells into the cell cycle in CDK4/6 sensitive, as well as resistant breast cancer tumor cells. I conducted Western blots to investigate if inhibition of CK1a resulted in the arrest of cells in the G1 phase of the cell cycle, by quantifying the levels of G1-phase Cyclins as well as S-phase Cyclins.
