Deng Lan, Zhao Le, Liu Lifen, Huang Haomin
R&D Department, Sunshine Guojian Pharmaceutical (Shanghai) Co. Ltd, a 3SBio Inc. Company, 399 Libing Road, Shanghai, 201203, China.
Open Life Sci. 2023 Jan 10;18(1):20220535. doi: 10.1515/biol-2022-0535. eCollection 2023.
Most patients with metastatic breast cancer or gastric cancer who are treated with trastuzumab, an anti-HER2 monoclonal antibody, become refractory to the drug within a year after the initiation of treatment. Although the combination of trastuzumab with pertuzumab produced synergetic effects in the treatment of HER2-overexpressing cancers, not all patients with HER2 overexpression benefited from the trastuzumab plus pertuzumab combination. To improve the clinical benefits of trastuzumab, we systemically investigated the combination of inetetamab (Cipterbin), an analog of trastuzumab, with a variety of small molecules, including tyrosine kinase inhibitors (TKIs) and chemotherapeutic agents . We showed that pan-TKIs-induced synergistic antitumor effects with inetetamab in the treatment of these two types of cancers and that adding chemotherapeutic agents to the existing TKI plus anti-HER2 monoclonal antibody combination strategies induced additional inhibitory effects, suggesting that such combination strategies may be choices for the treatment of these two tumors. Thus, combination therapies targeting distinct and broad pathways that are essential for tumor growth and survival can be effective for treating metastatic breast cancers and gastric cancers.
大多数接受抗HER2单克隆抗体曲妥珠单抗治疗的转移性乳腺癌或胃癌患者在开始治疗后一年内会对该药物产生耐药性。尽管曲妥珠单抗与帕妥珠单抗联合使用在治疗HER2过表达癌症中产生了协同效应，但并非所有HER2过表达患者都能从曲妥珠单抗加帕妥珠单抗联合治疗中获益。为了提高曲妥珠单抗的临床疗效，我们系统地研究了曲妥珠单抗类似物伊尼妥单抗（赛普汀）与多种小分子药物的联合使用，这些小分子药物包括酪氨酸激酶抑制剂（TKIs）和化疗药物。我们发现，泛TKIs与伊尼妥单抗联合使用在治疗这两种癌症时具有协同抗肿瘤作用，并且在现有的TKI加抗HER2单克隆抗体联合治疗策略中加入化疗药物可产生额外的抑制作用，这表明这种联合治疗策略可能是治疗这两种肿瘤的选择。因此，针对肿瘤生长和存活所必需的不同且广泛途径的联合疗法可有效治疗转移性乳腺癌和胃癌。
