Publication
Dual Modulators of p53 and Cyclin D in ER Alpha Signaling by Albumin Nanovectors Bearing Zinc Chaperones for ER-positive Breast Cancer Therapy
Publisher:
Bentham Science Publishers Ltd.
Date:
04-2021
DOI:
10.2174/1389557520999201124212347
Abstract: The inherited mutations and underexpression of BRCA1 in sporadic breast cancers resulting in the loss or functional inactivation of BRCA1 may contribute to a high risk of breast cancer. Recent researchers have identified small molecules (BRCA1 mimetics) that fit into a BRCA1 binding pocket within Estrogen Receptor alpha (ERα), mimic the ability of BRCA1 to inhibit ER& #945 activity, and overcome antiestrogen resistance. Studies indicate that most of the BRCA1 breast cancer cases are associated with p53 mutations. It indicates that there is a potential connection between BRCA1 and p53. Most p53 mutations are missense point mutations that occur in the DNA-binding domain. Structural studies have demonstrated that mutant p53 core domain misfolding, especially p53-R175H, is reversible. Mutant p53 reactivation with a new class of zinc metallochaperones (ZMC) restores WT p53 structure and functions by restoring Zn sup + /sup to Zn sup + /sup deficient mutant p53. Considering the role of WT BRCA1 and reactivation of p53 in tumor cells, our hypothesis is to target both tumor suppressor proteins by a novel biomolecule (ZMC). Since both proteins are present in the same cell and are functionally inactive, this state may be a novel efficacious therapeutic regime for breast cancer therapy. In addition, we propose to use Albumin Nanovector (ANV) formulation for target drug release.