Optimizing Treatment for NF1-Deficient Metastatic ER+ Breast Cancers
Abstract
This project centers on the NF1/neurofibromin tumor suppressor, which was best known as a GTPase Activating Protein (GAP) thatrepresses Ras activity. The parent grant has led to the discovery that NF1 has a GAP-independent activity by functioning also as a transcriptional co-repressor for estrogen receptor (ER) in ER+ breast cancer. Our data support the hypothesis that loss of a single tumor suppressor NF1 can enhance signaling activities from both the Ras and ER pathways, which must be properly co-targeted for efficient tumor inhibition. In this expansion award, our goal is to improve diagnose of NF1 loss in clinical samples in order to expand eligibility criteria for trials targeting ER+ breast cancer with NF1 loss. The specific aims are:AIM 1: To orthogonally validate genomic evidence for NF1 loss by develop a precise mass spectrometry (MS)-based diagnostic approach to accurately assess NF1 protein levels in core needle biopsy samples. The objective is to improve the diagnosis of NF1low state in the absence of detectable NF1 FS/NS mutation.AIM 2: To functionally characterize missense NF1 mutants recently identified in an adjuvant endocrine therapy trial as associated with poor prognosis to determine whether they should be included in the eligibility criteria for the present or future trials designed to improve outcomes in ER+ NF1low breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1190894
Entities
People
- Eric Chang
Organizations
- Baylor College of Medicine