Biochemistry, Microbiology and Immunology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.
J Cancer Res Clin Oncol. 2023 Jul;149(7):3701-3719. doi: 10.1007/s00432-022-04189-6. Epub 2022 Aug 17.
Breast cancer, the most prevalent cancer worldwide, consists of 4 main subtypes, namely, Luminal A, Luminal B, HER2-positive, and Triple-negative breast cancer (TNBC). Triple-negative breast tumors, which do not express estrogen, progesterone, and HER2 receptors, account for approximately 15-20% of breast cancer cases. The lack of traditional receptor targets contributes to the heterogenous, aggressive, and refractory nature of these tumors, resulting in limited therapeutic strategies.
Chemotherapeutics such as taxanes and anthracyclines have been the traditional go to treatment regimens for TNBC patients. Paclitaxel, docetaxel, doxorubicin, and epirubicin have been longstanding, Food and Drug Administration (FDA)-approved therapies against TNBC. Additionally, the FDA approved PARP inhibitors such as olaparib and atezolizumab to be used in combination with chemotherapies, primarily to improve their efficiency and reduce adverse patient outcomes. The immunotherapeutic Keytruda was the latest addition to the FDA-approved list of drugs used to treat TNBC.
The following review aims to elucidate current FDA-approved therapeutics and their mechanisms of action, shedding a light on the various strategies currently used to circumvent the treatment-resistant nature of TNBC cases.
The recent approval and use of therapies such as Trodelvy, olaparib and Keytruda has its roots in the development of an understanding of signaling pathways that drive tumour growth. In the future, the emergence of novel drug delivery methods may help increase the efficiency of these therapies whiel also reducing adverse side effects.
乳腺癌是全球最常见的癌症,它包括 4 个主要亚型,即 Luminal A、Luminal B、HER2 阳性和三阴性乳腺癌(TNBC)。三阴性乳腺癌肿瘤不表达雌激素、孕激素和 HER2 受体,约占乳腺癌病例的 15-20%。缺乏传统受体靶点导致这些肿瘤具有异质性、侵袭性和难治性,从而导致治疗策略有限。
紫杉醇、多西紫杉醇、多柔比星和表柔比星等化疗药物一直是 TNBC 患者的传统治疗方案。此外,FDA 还批准了 PARP 抑制剂,如奥拉帕利和阿替利珠单抗,与化疗联合使用,主要是为了提高其效率并减少不良的患者结局。免疫治疗药物 Keytruda 是最近被 FDA 批准用于治疗 TNBC 的药物之一。
本综述旨在阐明目前 FDA 批准的治疗方法及其作用机制,探讨目前用于规避 TNBC 治疗耐药性的各种策略。
最近批准和使用 Trodelvy、奥拉帕利和 Keytruda 等疗法的根源在于对驱动肿瘤生长的信号通路的理解的发展。未来,新型药物输送方法的出现可能有助于提高这些疗法的效率,同时减少不良反应。