Impact of Emergent Circulating Tumor DNA Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer.

The accumulation of emergent mutations during anti-EGFR therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine mutational status. This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded ctDNA mutations in panitumumab-treated patients.

Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells.

The AP-1B clathrin adaptor complex is responsible for the polarized transport of many basolateral membrane proteins in epithelial cells. Localization of AP-1B to recycling endosomes (REs) along with other components (exocyst subunits and Rab8) involved in AP-1B-dependent transport suggested that RE might be an intermediate between the Golgi and the plasma membrane. Although the involvement of endosomes in the secretory pathway has long been suspected, we now present direct evidence using four independent methods that REs play a role in basolateral transport in MDCK cells.

The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells.

The AP-1B clathrin adaptor complex plays a key role in the recognition and intracellular transport of many membrane proteins destined for the basolateral surface of epithelial cells. However, little is known about other components that act in conjunction with AP-1B. We found that the Rab8 GTPase is one such component.