Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma

By Xiaomo Jiang, Huai-Xiang Hao, J. Growney, Steve Woolfenden, Cindy Bottiglio, Nicholas Ng, Bo Lu, Mindy H. Hsieh, L. Bagdasarian, R. Meyer and 9 more. 2013

411 citations recorded by the source corpus.

Subfields: Genetics, Molecular Biology

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. W. de Lau
2. P. Gros
3. W. Peng
4. Peter W. Laird
5. Hui Shen
6. Chip Stewart
7. P. Park
8. Christopher Sander

In Molecular Biology

1. Peter W. Laird
2. Hui Shen
3. S. Baylin
4. Eric S. Lander
5. Timothy Triche
6. Gad Getz
7. W. de Lau
8. W. Peng

Citations in the corpus

• Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma (2017, positive): “RNF43 mutations have therapeutic implications (Figure S1B) (Jiang et al., 2013; Koo et al., 2015) and frequently occur in intraductal papillary mucinous neoplasm (IPMN) precursor lesions (Amato et al.”
• The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength (2014, positive): “Of interest, the small molecule Wnt secretion inhibitor LGK974 inhibits proliferation and induces differentiation of RNF43 mutant pancreatic adenocarcinoma cell lines even when tested in xenograft models (Jiang et al. 2013).”
• Wnt addiction of genetically defined cancers reversed by PORCN inhibition (2015, neutral): “9,17 Consistent with this hypothesis, there was massive remodeling of the transcriptome in RSPO-overexpressing CRC xenografts within 3 days of treatment.”
• Wnt/β-catenin signaling in cancers and targeted therapies (2021, background): “The LoF mutation of Znrf3/Rnf43 was reported to be oncogenic, and Porc inhibitors had shown a remarkable potency in this aspect.(27,124,278) Unfortunately, the absence of Apc is likely to induce a Wnt ligand-independent signaling, so tumors with Apc LoF mutations may be resistant to Porc inhibitors.”
• Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours (2021, background): “WNT974 exhibited preclinical activity in multiple tumour models, including Wnt-dependent head and neck cancer and RNF43-mutated pancreatic cancer xenografts.(7,12) Furthermore, dysregulated Wnt signalling has been linked to exclusion of T cells from the tumour microenvironment and resistance to immu”