Breast cancer is one of the world’s leading causes of oncological disease-related death. It is characterized by a high degree of heterogeneity on the clinical, morphological, and molecular levels. Based on molecular profiling breast carcinomas are divided into several subtypes depending on the expression of a number of cell surface receptors, e.g., ER, PR, and HER2. The Her2-positive subtype occurs in ~10–15% of all cases of breast cancer, and is characterized by a worse prognosis of patient survival. This is due to a high and early relapse rate, as well as an increased level of metastases. Several FDA-approved drugs for the treatment of Her2-positive tumors have been developed, although eventually cancer cells develop drug resistance. These drugs target either the homo- or heterodimerization of Her2 receptors or the receptors’ RTK activity, both of them being critical for the proliferation of cancer cells. Notably, Her2-positive cancers also frequently harbor mutations in the TP53 tumor suppressor gene, which exacerbates the unfavorable prognosis. In this review, we describe the molecular mechanisms of RTK-specific drugs and discuss new perspectives of combinatorial treatment of Her2-positive cancers through inhibition of the mutant form of p53.

乳腺癌是世界上肿瘤疾病相关死亡的主要原因之一。其特点是临床、形态和分子水平上高度异质性。根据分子谱分析，乳腺癌根据多种细胞表面受体（例如 ER、PR 和 HER2）的表达分为几种亚型。Her2 阳性亚型约占所有乳腺癌病例的 10-15%，其特点是患者生存预后较差。这是由于高且早期的复发率以及转移水平的增加。几种 FDA 批准的用于治疗 Her2 阳性肿瘤的药物已经被开发出来，尽管最终癌细胞会产生耐药性。这些药物针对 Her2 受体的同二聚或异二聚化或受体的 RTK 活性，这两者对于癌细胞的增殖都至关重要。值得注意的是，Her2 阳性癌症也经常存在 TP53 肿瘤抑制基因突变，这加剧了不良的预后。在这篇综述中，我们描述了 RTK 特异性药物的分子机制，并讨论了通过抑制 p53 突变形式组合治疗 Her2 阳性癌症的新视角。