AGER-dependent macropinocytosis drives resistance to KRAS-G12D-targeted therapy in advanced pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.

Multimodal Therapy May be Key to Improving Survival for Octogenarians Undergoing Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: An American Multicenter Analysis.

Background: As the population ages, the number of octogenarians with pancreatic ductal adenocarcinoma (PDAC) continues to rise. Morbidity and mortality following pancreatectomy have improved owing to safer surgery and better chemoradiation regimens. This study compares the outcomes and multimodality utilization in octogenarians (≥80 years) who underwent pancreaticoduodenectomy (PD) for PDAC, with a younger cohort.

Biotissue Curriculum Translates to Performance in the Operating Room for Gastrojejunostomy and Hepaticojejunostomy in Robotic Pancreaticoduodenectomy.

Objective: Robotic simulation training curricula aim to aid surgeons in attaining robotic operating room proficiency, but the crossover success remains to be examined.

Design: A retrospective cohort study grading robotic biotissue training models and intraoperative anastomotic videos. The curriculum included deliberate practice of inanimate drills of a hepaticojejunostomy (HJ) and gastrojejunostomy (GJ).

The effect of minimally invasive surgery on thirty-day postoperative outcomes of frail patients undergoing emergency colon resections.

Background: Frail patients have poor outcomes after emergent colon surgery. While minimally invasive surgery has shown improved outcomes in the general patient population undergoing colectomy, the benefits in frail patients are unknown.

Methods: We identified frail patients who underwent urgent or emergent colon resections from 2017 to 2021 in the National Surgical Quality Improvement Program database.

SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.

Direct targeting of the -mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.