Department of Microbiology and Immunology, Kampala International University, Western Campus, Box 20000, Uganda.
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea.
Pathol Res Pract. 2024 Nov;263:155607. doi: 10.1016/j.prp.2024.155607. Epub 2024 Sep 25.
Breast cancer is a heterogeneous disease with complex molecular pathogenesis. Overexpression of several tyrosine kinase receptors is associated with poor prognosis, therefore, they can be key targets in breast cancer therapy. Tyrosine kinase inhibitors (TKIs) have emerged as leading agents in targeted cancer therapy due to their effectiveness in disrupting key molecular pathways involved in tumor growth. TKIs target various tyrosine kinases, including the human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor receptor (VEGFR), anaplastic lymphoma kinase (ALK), vascular endothelial growth factor receptor (VEGFR)-associated multi-targets, rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), receptor tyrosine kinase-like orphan signal 1 (ROS1), Mitogen-activated protein kinase (MAPK), and tropomyosin receptor kinase (TRK). These drugs target the tyrosine kinase domain of receptor tyrosine kinases and play a vital role in proliferation and migration of breast cancer cells. Several TKIs, including lapatinib, neratinib, and tucatinib, have been developed and are currently used in clinical settings, often in combination with chemotherapy, endocrine therapy, or other targeted agents. TKIs have demonstrated remarkable benefits in enhancing progression-free and overall survival in patients with breast cancer and have become a standard of care for this population. This review provides an overview of TKIs currently being examined in preclinical studies and clinical trials, especially in combination with drugs approved for breast cancer treatment. TKIs have emerged as a promising therapeutic option for patients with breast cancer and hold potential for treating other breast cancer subtypes. The development of new TKIs and their integration into personalized treatment strategies will continue to shape the future of breast cancer therapy.
乳腺癌是一种具有复杂分子发病机制的异质性疾病。几种酪氨酸激酶受体的过度表达与预后不良相关，因此，它们可以成为乳腺癌治疗的关键靶点。由于其在破坏肿瘤生长中涉及的关键分子途径方面的有效性，酪氨酸激酶抑制剂 (TKI) 已成为靶向癌症治疗的主要药物。TKI 靶向各种酪氨酸激酶，包括人表皮生长因子受体 2 (HER2)、表皮生长因子受体 (EGFR)、血管内皮生长因子受体 (VEGFR)、间变性淋巴瘤激酶 (ALK)、血管内皮生长因子受体 (VEGFR)-相关多靶点、转染期间重排 (RET)、成纤维细胞生长因子受体 (FGFR)、受体酪氨酸激酶样孤儿信号 1 (ROS1)、丝裂原活化蛋白激酶 (MAPK) 和原肌球蛋白受体激酶 (TRK)。这些药物靶向受体酪氨酸激酶的酪氨酸激酶结构域，在乳腺癌细胞的增殖和迁移中发挥着重要作用。几种 TKI，包括拉帕替尼、奈拉替尼和图卡替尼，已经开发出来并在临床中使用，通常与化疗、内分泌治疗或其他靶向药物联合使用。TKI 已被证明在提高乳腺癌患者的无进展生存期和总生存期方面具有显著益处，并已成为该人群的标准治疗方法。本综述提供了目前在临床前研究和临床试验中检查的 TKI 的概述，特别是与批准用于乳腺癌治疗的药物联合使用的情况。TKI 已成为乳腺癌患者有前途的治疗选择，并有可能治疗其他乳腺癌亚型。新 TKI 的开发及其纳入个性化治疗策略将继续塑造乳腺癌治疗的未来。
