Dec 17, 2021 Uncategorized

OVERCOME THERAPEUTIC RESISTANCE IN ESTROGEN POSITIVE BREAST CANCER.

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

  1. No estrogen control
  2. Estrogen (E2) stimulation
  3. Fulvestrant alone (+E2)
  4. CDK4/6inhibitor alone (abemaciclib)  (+E2)
  5. Rac1 inhibitor alone (GYS32661) (+E2)
  6. Fulv + CDK4/6i (+E2)
  7. Fulv + Rac1i (+E2)
  8. CDK4/6i + Rac1i (+E2)
  9. Fulv + CDK4/6i + Rac1 I (+E2)

literature search : See references (last 10 years)

draft methodology:

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