Targeting Fatty Acid Synthase: A Mechanism-Guided Approach to Develop a Novel Therapeutic Intervention for Drug-Resistant Breast Cancer

Abstract

Resistance to trastuzumab and HER2-directed therapy remains an unmet clinical need for patients with HER2+ breast cancer, and currently there are no FDA-approved drugs that can reverse resistance to trastuzumab or other HER2-directed therapies. Our preliminary data show that Fatty Acid Synthase (FASN) plays a major role in the maintenance of an aggressive breast cancer phenotype, and that FASN inhibition reduces tumor growth and augments the cytotoxicity of trastuzumab and paclitaxel. In this proposal we will evaluate TVB-2640, a FASN inhibitor that targets cancer metabolism and inhibits breast cancer growth. We will conduct a phase II trial of TVB-2640 in combination with paclitaxel and trastuzumab in patients with metastatic breast cancer who have disease resistant to trastuzumab. We will evaluate the safety and clinical efficacy of TVB-2640, as well as the value of serum and tissue FASN as novel biomarkers of response in HER2+ breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2019
Accession Number
AD1129083

Entities

People

  • Ruth Lupu

Organizations

  • Mayo Clinic

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemotherapy
  • Clinical Trials
  • Drug Resistance
  • Fatty Acids
  • Inhibition
  • Inhibitors
  • Intervention
  • Lipids
  • Medical Personnel
  • Metabolism
  • Neoplasms
  • Programmed Cell Death
  • Resistance
  • Targeting
  • Therapy
  • Tumor Cell Line

Fields of Study

  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Medical Imaging.
  • Military Engineering.