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。目前的治疗选择有限的有效性，没有药物专门针对与转移有关的途径，因此迫切需要新的治疗方法。我们最近完成了一个3D球体的筛选，在基质细胞存在的情况下，临床上批准的药物，以确定那些可以重新用于阻止PC入侵。我们现在需要验证这些发现，并阐明抑制侵袭的分子机制。我们最成功的发现之一是抗纤维蛋白溶解，这是一个令人兴奋的新发现。我们的初步研究表明，这种抑制剂对癌细胞和基质细胞都有影响;我们现在需要解开分子通路，我们还想测试这种抑制剂是否能阻断PC细胞中的侵袭性伪足活动。侵袭伪足是促进侵袭的特殊癌细胞结构。该项目旨在将我们的筛选结果与我们在侵袭足生物学方面的现有专业知识结合起来，以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.