Gadi Vaishnavi, Shetty Saritha Rakesh
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMS Narsee Monjee Institute of Management Studies, Mumbai-56, Maharashtra, India.
Recent Adv Inflamm Allergy Drug Discov. 2022;16(2):60-76. doi: 10.2174/2772270816666220829090716.
Breast cancer is a global issue, affecting greater than 1 million women per annum. Over the past two decades, there have been numerous clinical trials involving the use of various pharmacological substances as chemopreventive agents for breast cancer. Various pre-clinical as well as clinical studies have established numerous anti-inflammatory molecules, including nonsteroidal anti-inflammatory drugs (NSAIDs) and dietary phytochemicals as promising agents for chemoprevention of several cancers, including breast cancer. The overexpression of COX-2 has been detected in approximately 40% of human breast cancer cases and pre-invasive ductal carcinoma in-situ lesions, associated with aggressive elements of breast cancer such as large size of the tumour, ER/PR negative and HER-2 overexpression, among others. Anti-inflammatory molecules inhibit COX, thereby inhibiting the formation of prostaglandins and inhibiting nuclear factor-κBmediated signals (NF-kB). Another probable explanation entails inflammation-induced degranulation, with the production of angiogenesis-regulating factors, such as vascular endothelial growth factor, which can be possibly regulated by anti-inflammatory molecules. Apart from NSAIDS, many dietary phytochemicals have the ability to decrease, delay, or stop the progression and/or incidence of breast cancer by their antioxidant action, regulating inflammatory and proliferative cell signalling pathways as well as inducing apoptosis. The rapid progress in chemoprevention research has also established innovative strategies that can be implemented to prevent breast cancer. This article gives a comprehensive overview of the recent advancements in using antiinflammatory molecules in the chemoprevention of breast cancer along with their mechanism of action, supported by latest preclinical and clinical data. The merits of anti-inflammatory chemopreventive agents in the prevention of cardiotoxicity have been described. We have also highlighted the ongoing research and advancements in improving the efficacy of using antiinflammatory molecules as chemopreventive agents.
乳腺癌是一个全球性问题，每年影响超过100万女性。在过去二十年中，有许多临床试验涉及使用各种药理物质作为乳腺癌的化学预防剂。各种临床前和临床研究已经确定了许多抗炎分子，包括非甾体抗炎药（NSAIDs）和膳食植物化学物质，它们是预防包括乳腺癌在内的几种癌症的有前景的药物。在大约40%的人类乳腺癌病例和原位导管癌前病变中检测到COX-2的过表达，这与乳腺癌的侵袭性因素有关，如肿瘤大小、ER/PR阴性和HER-2过表达等。抗炎分子抑制COX，从而抑制前列腺素的形成并抑制核因子-κB介导的信号（NF-κB）。另一种可能的解释是炎症诱导的脱颗粒，产生血管生成调节因子，如血管内皮生长因子，而抗炎分子可能对其进行调节。除了NSAIDs，许多膳食植物化学物质能够通过其抗氧化作用、调节炎症和增殖细胞信号通路以及诱导细胞凋亡来降低、延缓或阻止乳腺癌的进展和/或发病率。化学预防研究的快速进展也确立了可以实施的预防乳腺癌的创新策略。本文全面概述了在乳腺癌化学预防中使用抗炎分子的最新进展及其作用机制，并得到了最新临床前和临床数据的支持。还描述了抗炎化学预防剂在预防心脏毒性方面的优点。我们还强调了在提高使用抗炎分子作为化学预防剂的疗效方面正在进行的研究和进展。
