Precision Antibody-Based Synergistic Drug Combinations for Refractory Triple-Negative Breast Cancer

Abstract

Metastatic triple-negative breast cancer (mTNBC) represents an unmet clinical need. Our group recently led the clinical development of a new therapy for TNBC called sacituzumab govitecan (SG). Herein, we propose to capitalize on this treatment innovation. First is a laboratory based component that tests the mechanisms and effectiveness of specific drug combinations with SG, asking in part whether the combinations will work in multiple different TNBC models. Second is an animal-based component, in which we will test how effective the most promising combinations with SG are, how well-tolerated these combinations are, and whether staggered dosing schedules might preserve efficacy while minimizing side effects. Third is analysis of specimens from SG-treated patients, testing predicted biomarkers of response and resistance to SG, and using molecular analysis to discover new biomarkers. This analysis will highlight resistance mechanisms to SG and will help guide selection of TNBC patients who will benefit most from either single-agent SG or the new combinations.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2022
Accession Number
AD1169491

Entities

People

  • Aditva Bardia
  • Leif W Ellisen

Organizations

  • Massachusetts General Hospital

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemical Synthesis
  • Chemistry
  • Confocal Microscopy
  • Diseases And Disorders
  • Drug Combinations
  • Electronic Mail
  • Health Services
  • Institutional Review Board
  • Medical Personnel
  • Neoplasms
  • Oncology
  • Proteins

Fields of Study

  • Medicine

Readers

  • International Journalism and Media Studies.
  • Oncology
  • Oncology (Cancer Research).