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Article

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

Science translational medicine - 29 Jan 2025

Li Changfeng, Liu Yuanda, Liu Chang, Chen Fangquan, Xie Yangchun, Zeh Herbert J, Yu Chunhua, Liu Jiao, Tang Daolin, Kang Rui

Abstract excerpt

Pancreatic ductal adenocarcinoma (PDAC) driven by the KRAS-G12D 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. The up-regulation...

Read the complete abstract on PubMed

Topics

Pancreatic Neoplasms
Humans
Pinocytosis
Animals
Proto-Oncogene Proteins p21(ras)
Cell Line, Tumor

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Drug Resistance, Neoplasm

Mice

Apoptosis

Formins

Carcinoma, Pancreatic Ductal

Molecular Targeted Therapy

Mutation

Xenograft Model Antitumor Assays

Source

Identifiers

PMID: 39879317
DOI: 10.1126/scitranslmed.adp4986

Genes

AGER
KRAS
DIAPH1
HMGB1
RAC1

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 23 Oct 2026.

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