Project 50.1: Targeting pancreatic cancer invasion with novel therapeutics

胰腺癌（PC）的生存率非常低，由于转移性疾病的流行，很少有患者在诊断后存活超过5年。目前的治疗方案疗效有限，没有药物专门针对涉及转移的途径，因此迫切需要新的治疗方法。我们最近完成了一个三维球体筛选，在基质细胞存在的情况下，临床批准的药物可以识别那些可以重新用于阻止PC侵袭的药物。我们现在需要验证这些命中并阐明支持抑制入侵的分子机制。我们最热门的产品之一是抗纤溶药物，这是一个令人兴奋的新发现。我们的初步数据表明对癌症和基质细胞都有影响；我们现在需要解开分子途径。我们还想测试这种抑制剂是否能阻断PC细胞的非过继体活性。侵殖体是一种特殊的癌细胞结构，可以促进癌细胞的侵袭。该项目旨在将我们的筛查发现与我们现有的侵入性生物学专业知识结合起来，开发针对胰腺癌侵袭的新疗法。

Pancreatic cancer (PC) survival is devastatingly low with few patients surviving more than 5 years postdiagnosis due to the prevalence of metastatic disease. Currently treatment options have limitedefficacy with no drugs specifically targeting the pathways implicated in metastasis and thus noveltherapeutic approaches are urgently required. We have recently completed a 3D spheroid screen, inthe presence of stromal cells, of clinically approved drugs to identify those that can be repurposed toblock PC invasion. We now need to validate these hits and elucidate the molecular mechanism thatunderpins suppression of invasion.One of our top hits was an anti-fibrinolytic, an exciting and novel discovery. Our preliminary datasuggests impacts on both cancer and stromal cells; we now need to untangle the molecular pathways.We also want to test if this inhibitor blocks invadopodia activity in PC cells. Invadopodia are specialisedcancer cell structures that facilitate invasion. This project aims to bring together our screen discoverieswith our existing expertise in invadopodia biology to develop novel therapeutics to target pancreaticcancer invasion.