Gene-drug interactions in the melanocyte lineage and melanoma

我们工作的目的是发现治疗黑色素瘤的新方法和药物靶点。黑色素瘤是最致命的皮肤癌，在英国和欧洲的发病率持续快速上升。最近黑色素瘤治疗的进展往往会导致癌症的消退，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具有抵抗力。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，可以与当前的治疗方法结合使用来根除肿瘤。我们已经开发了一个模型系统，使我们能够通过基因工程使斑马鱼患上类似于人类黑色素瘤的黑色素瘤。我们使用这些动物来成像黑色素瘤中不同的细胞类型，筛选新的药物，并在单细胞水平上跟踪癌症中的不同细胞群体对新药物的反应。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，并确定我们可以用来针对黑色素瘤的新的脆弱性。

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.