Homegrown solutions in Viet Nam: bringing C. asiatica compounds forward as candidates to treat liver cancer

肝癌是越南的一个严重问题，每年导致2.5万越南人死亡，比任何其他癌症都要多。这个问题在越南尤其严重，因为重叠的危险因素趋于一致：乙型和丙型肝炎普遍存在；酒精消费量非常高；越南战争期间使用橙剂导致二恶英在环境中持续存在；文化和经济因素意味着，患者往往只在非常晚期才去寻求现代医学治疗，首先依靠传统的草药疗法。然而，越南也提供了独特的机会。它的传统医学很大程度上是经验性的，即基于经验而不是哲学信念。因此，有机会发现具有治疗效果的天然产品，这些产品可以通过化学和生物学的知情方式开发为批准的药物。积雪草（Centella asiatica）是一种受欢迎的草药，我们的越南合作伙伴发现其天然产物之一madecassic酸对肝癌有活性，其化学衍生物显示出进一步改善的潜力。在这个项目中，我们将在若干方面开展工作，将合成酸衍生物作为治疗肝癌的潜在新疗法，并在越南生产。这包括优化生长条件以最大限度地生产合成酸（使用分析化学），改进化学提取工艺，扩大手头化学衍生物的范围，使用化学生物学对合成酸的细胞效应进行深入研究，以及探索使用聚合物来控制体内释放速率。这项工作将通过与越南利益攸关方（医生、实业家、农民、决策者）的网络活动以及评估人口对跨越传统与现代鸿沟的药物的态度的调查工作得到强调和支持。

Liver cancer is a critical problem in Viet Nam, killing 25 thousand Vietnamese individuals each year - more than any other cancer. The problem is especially acute in Viet Nam because of the convergence of overlapping risk factors: hepatitis B and C are prevalent; alcohol consumption is very high; dioxins persist in the environment stemming from the use of Agent Orange during the Viet Nam War; and cultural and economic factors mean that patients frequently present for modern medicine only at a very advanced stage, relying first on traditional herbal remedies. However, Viet Nam also presents unique opportunities. Its traditional medicine is largely empirical i.e. based on experience rather than philosophical convictions. There is therefore opportunity for the discovery of natural products with therapeutic efficacy, which could be developed as approved drugs in an informed way through chemistry and biology. Centella asiatica is a popular medicinal herb, and our Vietnamese partners have discovered that one of its natural products, madecassic acid, is active against liver cancer, with chemical derivatives showing further improved potential. In this project we will work on a number of fronts to bring madecassic acid derivatives forward as potential new therapeutics against liver cancer, which could be produced within Viet Nam. This involves optimisation of growth conditions for maximal madecassic acid production (using analytical chemistry), improvement of chemical extraction processes, broadening the range of chemical derivatives in hand, in-depth studies using chemical biology of the cellular effects of madecassic acid, and exploration of use of polymers to control the rate of release in the body. This work will be underlined and supported by networking activities with stakeholders (doctors, industrialists, farmers, policy makers) in Viet Nam, and survey work to assess attitudes of the population to medicines which cross over the traditional-modern divide.