Development of Specific Inhibitors for Breast Cancer-Associated Variants of ErbB2

Abstract

The receptor tyrosine kinase HER2/ErbB2 is one of the most highly mutated tyrosine kinases in breast cancer. Several mutations within the ErbB2 kinase domain have been identified in breast cancer patients, but in most cases it is not known whether these mutations increase kinase activity and signaling. The first objective of this project is to provide data linking ErbB2 mutations to their degree of kinase activation. The second objective is to use computational screening methods to identify compounds that can selectively target and inhibit those ErbB2 mutants verified as active. The third objective is to experimentally test a subset of the most promising compounds for the ability to experimentally inhibit specific ErbB2 mutants. The research team consists of two principal investigators at the same institution: Dr. Todd Miller (Initiating PI, Grant Number BC132617) whom has expertise in tyrosine kinase signaling, and Dr. Robert C. Rizzo (Partnering PI, Grant Number, BC132617P1) whom has expertise in computational modeling procedures. This report, prepared by Partnering PI Rizzo and his team, will primarily focus on the computational progress. The Initiating PI Miller has submitted a separate report.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2015
Accession Number
ADA624304

Entities

People

  • Robert C Rizzo

Organizations

  • State University of New York

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Amino Acids
  • Biomedical Research
  • Breast Cancer
  • Chemical Compounds
  • Computational Modeling
  • Computational Science
  • Electronic Mail
  • Inhibitors
  • Kinases
  • Molecular Dynamics
  • Mutations
  • Neoplasms
  • Simulations
  • Small Molecules
  • Students
  • Tyrosine

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and genetic basis of cancer.
  • Research Science/Academic Research