Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer.

ABSTRACT: Netrin-1 is upregulated in cancers as a protumoural mechanism¹. Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas (ECs) and demonstrate that netrin-1 blockade, using an anti-netrin-1 antibody (NP137), is effective in reduction of tumour progression in an EC mouse model. We next examined the efficacy of NP137, as a first-in-class single agent, in a Phase I trial comprising 14 patients with advanced EC. As best response we observed 8 stable disease (8 out of 14, 57.1%) and 1 objective response as RECIST v.1.1 (partial response, 1 out of 14 (7.1%), 51.16% reduction in target lesions at 6 weeks and up to 54.65% reduction during the following 6 months). To evaluate the NP137 mechanism of action, mouse tumour gene profiling was performed, and we obse

SUBMITTER: Cassier PA 

PROVIDER: S-EPMC10412451 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature