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.

散发性乳腺癌中 BRCA1 的遗传突变和低表达导致 BRCA1 的丢失或功能失活可能导致患乳腺癌的高风险。最近的研究人员已经确定了小分子（BRCA1 模拟物），它们可以装入雌激素受体 α (ERα) 内的 BRCA1 结合口袋，模拟 BRCA1 抑制 ERα 活性的能力，并克服抗雌激素抗性。研究表明，大多数 BRCA1 乳腺癌病例都与 p53 突变有关。这表明 BRCA1 和 p53 之间存在潜在的联系。大多数 p53 突变是发生在 DNA 结合域中的错义点突变。结构研究表明，突变 p53 核心域错误折叠，尤其是 p53-R175H，是可逆的。²⁺到 Zn ²⁺缺陷突变体 p53。考虑到 WT BRCA1 的作用和 p53 在肿瘤细胞中的重新激活，我们的假设是通过一种新型生物分子 (ZMC) 靶向这两种肿瘤抑制蛋白。由于这两种蛋白质都存在于同一细胞中并且在功能上处于非活性状态，因此这种状态可能是一种新型有效的乳腺癌治疗方案。此外，我们建议使用白蛋白纳米载体 (ANV) 制剂进行靶向药物释放。