Repurposing of Macrolide Antibiotic Clarithromycin for the Prevention of Lung and Breast Cancer

大环内酯类抗生素克拉霉素的再利用用于预防肺癌和乳腺癌

• 批准号: 10020558
• 负责人: Powel Brown
• 金额: $ 91.9万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2022-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020558
• 关键词: Animal Model; Anti-inflammatory; Antineoplastic Agents; B-Cell Lymphomas; Bacterial Infections; Bioavailable; Biological Markers; Breast Adenocarcinoma; Breast Cancer Model; Breast Cancer Prevention; Clarithromycin; Clinical; Clinical Trials; Cytotoxic T-Lymphocytes; Dose; HIV; Helicobacter Infections; Immunomodulators; Infection; Infectious Skin Diseases; Intravenous; Lewis Lung Carcinoma; Light; Lung; Macrolide Antibiotics; Malignant Epithelial Cell; Malignant neoplasm of lung; Multiple Myeloma; Mus; Mycobacterium avium Complex; Nodule; Non-Small-Cell Lung Carcinoma; Oral; Patients; Prevention; Property; Prospective Studies; Rattus; Refractory; Research; Respiratory System; Stomach; T-Lymphocyte Subsets; Toxic effect; Travel; Ulcer; Vascular Endothelial Growth Factors; cancer prevention; cost; efficacy testing; immunoregulation; lung cancer prevention; malignant breast neoplasm; malignant stomach neoplasm; prevent; soft tissue; subcutaneous; tumor

Clarithromycin (CAM) is a broad-spectrum macrolide antibiotic used to treat bacterial infections of the skin, soft tissue, and respiratory tract; to treat and prevent disseminated Mycobacterium avium complex infections in people with human immunodeficiency virus; and to eradicate ulcer-causing gastric Helicobacter pylori infections. It is low-cost, orally bioavailable, and has a low toxicity profile, even when administered for 4 years at a dose of 200 mg/day. Due to its strong anti-inflammatory, immunomodulatory, and anti-angiogenic properties, including the suppression of NFκB, the expansion of anti-tumor natural killer T cell subsets, and the reduction of VEGF, CAM has been identified as one of the most promising candidates for repurposing as an anti-cancer drug. In the clinical setting, it completely regressed high-grade gastric B-cell lymphoma, and showed efficacy in the treatment of naïve and refractory multiple myeloma when combined with other immunomodulatory drugs. In light of this, there are numerous ongoing clinical trials testing the efficacy of CAM in the prevention and treatment of gastric cancer, MALT, and other B-cell lymphomas. The purpose of this Task Order is to test the efficacy of CAM in the prevention of breast and lung cancer. CAM has been shown to increase the overall survival of rats and mice inoculated subcutaneously with mammary adenocarcinoma and Lewis lung carcinoma (LLC) cells, respectively, and to reduce the number of tumor nodules in the lungs of mice intravenously injected with LLC cells. In a prospective study, CAM has also been shown to significantly increase the overall survival of patients with advanced non-small cell lung cancer, extending their lives from 277 to 535 days.

克拉霉素 (CAM) 是一种广谱大环内酯类抗生素，用于治疗皮肤、软组织和呼吸道的细菌感染；治疗和预防人类免疫缺陷病毒患者的播散性鸟分枝杆菌复合感染，并根除引起胃溃疡的药物；它成本低廉，口服生物利用度高，毒性低，即使以 4 年剂量服用也是如此。 200 毫克/天。 由于其强大的抗炎、免疫调节和抗血管生成特性，包括抑制 NFκB、扩大抗肿瘤自然杀伤 T 细胞亚群以及减少 VEGF，CAM 已被认为是最有前途的药物之一在临床环境中，它完全消退了高级别胃 B 细胞淋巴瘤，并在与其他药物联合治疗初治和难治性多发性骨髓瘤时显示出疗效。鉴于此，目前有大量临床试验正在测试 CAM 在预防和治疗胃癌、MALT 和其他 B 细胞淋巴瘤方面的功效。 该任务顺序的目的是测试 CAM 在预防乳腺癌和肺癌方面的功效。 CAM 已被证明可以提高分别皮下接种乳腺癌和 Lewis 肺癌 (LLC) 细胞的大鼠和小鼠的总体存活率。 ，并减少静脉注射 LLC 细胞的小鼠肺部肿瘤结节的数量。在一项前瞻性研究中，CAM 还被证明可以显着提高晚期非小细胞肺患者的总体生存率。癌症，将他们的生命从 277 天延长至 535 天。