Pyrvinium Pamoate

来自奥克兰大学等机构的科学家们通过研究发现，一种以新的组合方式使用的古老药物或在治疗肠癌上能表现出良好的疗效。 10%的结直肠癌肿瘤都携带有BRAF V600E突变，这就表明，靶向作用BRAF或许有望作为一种潜在的疗法。然而，BRAF抑制剂在这种情况下只有有限的单剂可供使用，BEACON临床试验揭示了组合性疗法的潜力，即利用西妥昔单抗(cetuximab)来靶向作用EGF受体或能明显增强BRAF抑制剂在BRAF突变的结直肠癌治疗过程中的疗效。 近日，一篇发表在国际杂志Molecular Cancer Therapeutics上题为“Response to BRAF targeted therapy is enhanced by co-targeting VEGFRs or WNT/β-Catenin signaling in BRAF-mutant colorectal cancer models”的研究报告中，来自奥克兰大学等机构的科学家们通过研究发现，一种以新的组合方式使用的古老药物或在治疗肠癌上能表现出良好的疗效。 研究者Peter Shepherd教授说道：“尽管近年来科学家们在开发肠癌新型疗法上取得了长足的进展，但新型疗法的开发仍然是非常昂贵且耗时的，作为这一问题的一种可能性的解决方案，研究人员一直在调查是否能以一种新的方式来利用老药提供一种更快速且便宜的方式来治疗人类肠癌。文章中，研究人员调查了几种专利即将过期的癌症药物，当他们将其中两种药物结合后结果发现，在实验室研究中，药物组合能明显增强治疗肠癌或结直肠癌的总体疗效。” 对癌症发生机制的理解或许也能促进本文研究的进行。近些年来，科学家们通过不断深入的研究揭示了结直肠癌发生的分子机制，尤其是，某些疾病亚型依赖于小血管的发展以及被称之为BRAF和β-连环蛋白的特殊蛋白。如今研究人员识别出了能靶向作用这些蛋白的现有药物，同时还调查了将这些药物组合起来提供强大的抗癌效率的潜力和可能性。 图片来源：https://aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-21-0941/709616/Response-to-BRAF-targeted-therapy-is-enhanced-by 研究者表示，两种老药或许就表现出了强大的潜力，其中一种是抗癌药物阿昔替尼(axitinib)，另一种则是恩波维铵（pyrvinium），其是科学家们20世纪60年代所开发的一种治疗蛲虫的廉价药物，如今研究人员认为其能被重新用于治疗癌症；在一组研究中，研究人员发现了名为维莫非尼（vemurafenib）的药物在靶向作用BRAF上的效率，当加入药物阿昔替尼后就能增强维莫非尼的作用效果，阿昔替尼能通过减少小血管的生长来发挥作用。 在其它情况下，这些药物都能用于治疗其它类型的癌症，而且其很快也会失去专利的保护，因此在后期治疗过程中其成本将会大大降低。在第二组研究中，研究人员发现证据表明，能靶向作用β-连环蛋白的药物恩波维铵能增加药物维莫非尼的疗效。 研究者Khanh Tran博士说道，已经存在的药物或许能被重新定向用来治疗多种类型的癌症，这或许能大大降低癌症疗法的费用。 由于这些药物已经用于其它疗法目的，这或许就使得科学家们进行临床试验更加容易，从而就能揭示相关研究结果是否真的能转化为改善患者的治疗结局。下一步研究人员将计划进行一项随机对照的临床试验。综上，本文研究结果表明，临床前研究数据揭示，在结直肠癌治疗过程中BRAF抑制剂的疗效或许能被小分子抑制剂共同靶向作用WNT/β-连环蛋白或VEGFRs来提高。（生物谷Bioon.com） 原始出处： Khanh B. Tran，Sharada V. Kolekar，Qian Wang, et al. Response to BRAF targeted therapy is enhanced by co-targeting VEGFRs or WNT/β-Catenin signaling in BRAF-mutant colorectal cancer models, Molecular Cancer Therapeutics (2022). DOI: 10.1158/1535-7163.MCT-21-0941

New combinations and formulations of older therapies are showing promise for the treatment of bowel cancer, researchers have found. Old medicines, combined in new ways, are showing promise for treating bowel cancer, a group of University of Auckland researchers has found. "While there have been advances in treatments for this disease in recent years, the development of new medicines is expensive and time-consuming," lead researcher Professor Peter Shepherd says. "As a possible solution to this problem, our group has been investigating whether using old drugs in new ways could provide a faster and cheaper way of treating this disease." The scientists investigated several cancer drugs that are coming off patent soon. When they combined two such drugs, they found greatly enhanced overall effectiveness in treating bowel, or colorectal, cancer in their lab-based studies. Developments in our understanding of how cancers function have paved the way for this research, Shepherd says. "In recent years, research has led to a rapid increase in our understanding of how colorectal cancer develops. In particular, some sub-types of the disease rely on the development of small blood vessels and on proteins called BRAF and beta-catenin. "The research group identified existing drugs that target these and investigated the possibility that combining them could have powerful anti-cancer effects." Studies in the labs at the University of Auckland have shown strong promise for two older drugs. One is an anticancer drug called axitinib. The other is pyrvinium, a low-cost drug that was developed in the 1960s to treat threadworm, which the researchers believe could be reformulated for use in cancer treatment. In one set of studies, the researchers found that the efficacy of another older drug targeting BRAF, called vemurafenib, could be greatly enhanced by adding axitinib. Axitinib works by reducing the growth of small blood vessels. Both these drugs are used in other contexts to treat other types of cancer and will soon be off patent and so the cost of using them in treatment will drop greatly, Shepherd says. In a second set of studies, the group found evidence that pyrvinium, which targets beta-catenin, could also increase the efficacy of vemurafenib. Dr Khanh Tran who performed most of the experiments says, "This work suggests that existing drugs might be able to be repurposed to treat this type of cancer which could significantly reduce the cost of such therapy." Tran says, "Since the drugs we used are already in use for other purposes, it makes it much easier to develop clinical trials to see how the findings of our studies will actually translate to improved outcomes for patients with this disease." The HRC provided $1.2 million over three years for this research and the Gut Cancer Foundation supported this with an additional $150,000. Next the researchers are planning a randomised, controlled clinical trial.