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

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携带者的播散性禽分枝杆菌复合感染；以及根除引起溃疡的胃幽门螺杆菌感染。它成本低，口服生物利用度高，毒性低，即使以每天200毫克的剂量给药4年也是如此。 由于其强大的抗炎、免疫调节和抗血管生成特性，包括抑制核因子κB、扩增抗肿瘤自然杀伤T细胞亚群、降低血管内皮生长因子，已被认为是最有前途的抗癌药物之一。在临床环境中，它完全消退了高度恶性的胃B细胞淋巴瘤，并在与其他免疫调节药物联合治疗初治和难治性多发性骨髓瘤时显示出疗效。有鉴于此，有许多正在进行的临床试验测试CAM在预防和治疗胃癌、MALT和其他B细胞淋巴瘤方面的有效性。 本任务单的目的是测试CAM在预防乳腺癌和肺癌方面的效果。研究表明，CaM可提高皮下接种乳腺癌和Lewis肺癌(LLC)细胞的大鼠和小鼠的总存活率，并减少静脉注射LLC细胞的小鼠肺内肿瘤结节的数量。在一项前瞻性研究中，CAM还被证明可以显著提高晚期非小细胞肺癌患者的总体存活率，将他们的寿命从277天延长到277天。

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.