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 ERα 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 Zn2+ to Zn2+ 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.
Keywords: Breast cancer, BRCA1, ERα, ZMC, albumin nano vectors, p53.
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