Pancreatic cancer cachexia is mediated by PTHrP-driven disruption of adipose <i>de novo</i> lipogenesis.

ABSTRACT: Pancreatic cancer patients have the highest rates and most severe forms of cancer cachexia, yet cachexia etiologies remain largely elusive, leading to a lack of effective intervening therapies. Parathyroid hormone-related protein (PTHrP) has been clinically implicated as a putative regulator of cachexia, with serum PTHrP levels correlating with increased weight loss in PDAC patients. Here we show that cachectic PDAC patients have high expression of tumor PTHrP and use a genetically engineered mouse model to functionally demonstrate that loss of PTHrP blocks cachectic wasting, dramatically extending overall survival. The re-expression of PTHrP in lowly cachectic models is sufficient to induce wasting and reduce survival in mice, which is reversed by the conditional deletion of the PTHrP rec

SUBMITTER: Bhalerao N 

PROVIDER: S-EPMC12157458 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature