Humanized anti-DEspR IgG4^S228P antibody increases overall survival in a pancreatic cancer stem cell-xenograft peritoneal carcinomatosis rat^nu/nu model.

ABSTRACT:

Background

Pancreatic peritoneal carcinomatosis (PPC), with the worst median overall-survival (mOS), epitomizes the incurability of metastatic cancer. Cancer stem cells (CSCs) underpin this incurability. However, inhibitors of CSC-stemness fail to increase mOS in cancer patients despite preclinical tumor-reduction. This shortfall reinforces that preclinical efficacy should be defined by increased mOS in the presence of cancer comorbidities, CSC-heterogeneity and plasticity. The primary objectives of this study are: to test the dual endothelin-1/signal peptide receptor, DEspR, as a nodal therapeutic target in PPC, given DEspR induction in anoikis-resistant pancreatic CSCs, and to validate humanized anti-DEspR antibody, hu-6g8, as a potential therapeutic for PPC.

Methods

We us

SUBMITTER: Gromisch CM 

PROVIDER: S-EPMC8048286 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature