THE ROLE OF INHIBITING RAC 1 TO OVERCOME THERAPEUTIC RESISTANCE IN ESTROGEN POSITIVE BREAST CANCER.
background : Discuss
objectives : Discuss
Objective 1: determine single-agent IC50 concentrations for Fulvestrant, CDK4/6 inhibitor (abemaciclib), Rac1 inhibitor (GYS32661) in wild type (WT) and mutant ESR1 (Y527S, D538G) MCF7 cell line, and determine effects on ER-mediated gene expression in the mutant cells
- Skills involved: cell culture, drug dilution, proliferation assays, PCR + RTqPCR
*Sub objective: determine Rac1 activity in WT, ESR1 mutant cell lines treated +/- IC50 of agents
Objective 2: Determine the combinatorial efficacy of fulvestrant +/- CDk4/6 inhibitor +/- Rac1 inhibitor in WT and mutant ESR1 MCF7 cells on cell proliferation, 2D colony formation, 3D colony formation
- No estrogen control
- Estrogen (E2) stimulation
- Fulvestrant alone (+E2)
- CDK4/6inhibitor alone (abemaciclib) (+E2)
- Rac1 inhibitor alone (GYS32661) (+E2)
- Fulv + CDK4/6i (+E2)
- Fulv + Rac1i (+E2)
- CDK4/6i + Rac1i (+E2)
- Fulv + CDK4/6i + Rac1 I (+E2)
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