Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve Is a Therapeutic Strategy for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent growth. Inhibition of the KRAS-RAF-MEK-ERK pathway enhances autophagic flux and dependency, and concurrent treatment with the nonspecific autophagy inhibitor chloroquine (CQ) and ERK-MAPK pathway inhibitors can synergistically block PDAC growth. However, CQ is limited in terms of specificity and potency.

Un-FASN-ing cancer's seat belt: Linking lipid metabolism and antigen presentation.

MHC-II expression on cancer cells is associated with improved treatment outcome. In this issue, Huang et al. report a panel of small molecules that selectively upregulate MHC-II on cancer cells through suppression of fatty acid synthase (FASN), resulting in inhibition of tumor growth.

A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation.

Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model.