Maya Mileski
Pronouns: She/Her
Research Mentor(s): Alnawaz Rehemtulla
Research Mentor School/College/Department: Radiation Oncology / Medicine
Program: UROP
Session: Session 1 (9:00am – 9:50am)
Authors: Maya Mileski, Maya Mileski, Alnawaz Rehemtulla, Sahezeel Awadia
Abstract
Breast cancer impacts millions of women throughout the world. Estrogen receptor-positive (ER+) breast cancer is the most common form of breast cancer. Antiestrogens were the first therapy aimed at treating this subtype, but resistance to these warranted the development of CDK4/6 inhibitors to address this problem by halting cell cycle progression in ER+ cells. This treatment has proven to be successful in the clinic, but resistance to CDK4/6 inhibitors is also common. My research will explore the role of the protein FADD (Fas Associated Death Domain) in promoting the development of CDK4/6 inhibitor resistance. Specifically, my lab has shown that the phosphorylated form of FADD is an alternate pathway for cancer cells to progress through the cell cycle, thereby promoting CDK4/6 resistance. Since CK1a is the kinase that phosphorylates FADD, I will use CK1a inhibitors BTX-161 and BTXA58 to treat both sensitive and resistant MCF7 breast cancer cells. This process will involve treatment with these drugs, then performing a Western Blot to analyze phosphorylation of FADD. With this data, I have been able to show the changes in CK1a levels and/or activity result in loss of FADD-phosphorylation. A decreases in FADD-phosphorylation in CK1a inhibited cells restores sensitivity to CDK4/6 inhibitors in resistant breast cancer cells. Further investigation of these findings in the coming months will help us gain a more full understanding of the role of FADD, and if this can then be implemented into treatments that will better fight breast cancer and save many lives.
