Tolba M F, Elghazaly H, Bousoik E, Elmazar M M A, Tolaney S M
Department of Pharmacology and Toxicology, Faculty of Pharmacy and Center of Drug Discovery Research and Development, Ain Shams University, Cairo, 11566, Egypt.
School of Life and Medical Sciences, University of Hertfordshire-Hosted By Global Academic Foundation, New Capital City, Egypt.
Clin Transl Oncol. 2021 Oct;23(10):1979-1994. doi: 10.1007/s12094-021-02613-w. Epub 2021 Apr 19.
The year 2019 witnessed the first approval of an immune checkpoint inhibitor (ICI) for the management of triple negative breast cancers (TNBC) that are metastatic and programmed death ligand (PD)-L1 positive. Extensive research has focused on testing ICI-based combinatorial strategies, with the ultimate goal of enhancing the response of breast tumors to immunotherapy to increase the number of breast cancer patients benefiting from this transformative treatment. The promising investigational strategies included immunotherapy combinations with monoclonal antibodies (mAbs) against human epidermal growth factor receptor (HER)-2 for the HER2 + tumors versus cyclin-dependent kinase (CDK)4/6 inhibitors in the estrogen receptor (ER) + disease. Multiple approaches are showing signals of success in advanced TNBC include employing Poly (ADP-ribose) polymerase (PARP) inhibitors, tyrosine kinase inhibitors, MEK inhibitors, phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) signaling inhibitors or inhibitors of adenosine receptor, in combination with the classical PD-1/PD-L1 immune checkpoint inhibitors. Co-treatment with chemotherapy, high intensity focused ultrasound (HIFU) or interleukin-2-βɣ agonist have also produced promising outcomes. This review highlights the latest combinatorial strategies under development for overcoming cancer immune evasion and enhancing the percentage of immunotherapy responders in the different subsets of advanced breast cancers.
2019年，免疫检查点抑制剂（ICI）首次获批用于治疗转移性且程序性死亡配体（PD）-L1阳性的三阴性乳腺癌（TNBC）。广泛的研究集中在测试基于ICI的联合策略，其最终目标是增强乳腺肿瘤对免疫疗法的反应，以增加受益于这种变革性治疗的乳腺癌患者数量。有前景的研究策略包括针对HER2+肿瘤的免疫疗法与抗人类表皮生长因子受体（HER）-2单克隆抗体（mAb）联合，以及针对雌激素受体（ER）+疾病的细胞周期蛋白依赖性激酶（CDK）4/6抑制剂联合。在晚期TNBC中，多种方法显示出成功的迹象，包括使用聚（ADP-核糖）聚合酶（PARP）抑制剂、酪氨酸激酶抑制剂、MEK抑制剂、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）信号抑制剂或腺苷受体抑制剂，与经典的PD-1/PD-L1免疫检查点抑制剂联合使用。与化疗、高强度聚焦超声（HIFU）或白细胞介素-2-βɣ激动剂联合治疗也产生了有前景的结果。本综述重点介绍了正在开发的最新联合策略，以克服癌症免疫逃逸并提高晚期乳腺癌不同亚组中免疫疗法应答者的比例。
