Gene-drug interactions in the melanocyte lineage and melanoma

我们工作的目的是发现黑色素瘤的新治疗方法和药物靶点。黑色素瘤是皮肤癌中最致命的一种，在英国和欧洲的发病率持续快速上升。黑色素瘤治疗的最新进展通常会导致癌症消退，但对大多数患者来说，黑色素瘤会复发。这表明，虽然治疗可以杀死大多数癌症，但黑色素瘤中有一些细胞对治疗有抵抗力。我们的目标是在黑色素瘤中识别这些不同的细胞，并开发新的治疗方法，可以与目前的治疗方法结合使用，以根除肿瘤。我们已经开发了一个模型系统，使我们能够对斑马鱼进行基因工程改造，使其产生与人类黑色素瘤相似的黑色素瘤。我们使用这些动物来成像黑色素瘤中的不同细胞类型，筛选新药，并在单细胞水平上跟踪癌症中不同细胞群对新药的反应。没有其他动物系统允许我们在这个分辨率下进行这些研究。我们希望这些研究将帮助我们更好地了解黑色素瘤对药物治疗的反应，并确定我们可以用于靶向黑色素瘤的新漏洞。

The aim of our work is to discover new therapeutic approaches and drug targets for melanoma. Melanoma is the most deadly form of skin cancer, and incidence continues to rise rapidly in the UK and Europe.Recent advances in melanoma therapy often lead to regression of the cancer, but for most patients, the melanoma comes back. This suggests that while therapies can kill most of the cancer, there are some cells in the melanoma that are resistant to therapy. Our goal is to identify these different cells within melanoma, and develop new therapeutic approaches that can be used in combination with current therapy to eradicate the tumour. We have developed a model system that enables us to genetically engineer zebrafish to develop melanomas that are similar to human melanomas. We use these animals to image the different cell types within melanoma, to screen for new drugs, and follow how the different cell populations within the cancers respond to new drugs at the single cell level. There are no other animal systems that allow us to do these studies at this resolution. We hope that these studies will help us to better understand how melanoma responds to drug treatment, and identify new vulnerabilities that we can use to target melanoma.