Dataset Information



ABSTRACT: Strong activation of the oncogenic Wnt/beta-catenin pathway is a main mechanism of resistance to FOXO3a-induced apoptosis promoted by PI3K and AKT inhibitors in colorectal cancer (CRC). Reducing Wnt/beta-catenin activity would sensitize colorectal tumors to these inhibitors. However, no Wnt/beta-catenin signaling inhibitor has proven clinical potential yet. Recently, inhibitors that block tankyrases were shown to reduce colon cancer cell proliferation by decreasing nuclear beta-catenin. We aim to identify determinants of response to these novel Wnt-inhibitors. Therefore, we treated in vivo three different patient-derived xenograft models (PDX; P2, P5 and P30) growing subcutaneously in NOD SCID mice with the novel tankyrase inhibitor NVP-TNKS656.

ORGANISM(S): Homo sapiens

SUBMITTER: Stephan Tenbaum 

PROVIDER: E-MTAB-2446 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Tankyrase Inhibition Blocks Wnt/β-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer.

Arqués Oriol O   Chicote Irene I   Puig Isabel I   Tenbaum Stephan P SP   Argilés Guillem G   Dienstmann Rodrigo R   Fernández Natalia N   Caratù Ginevra G   Matito Judit J   Silberschmidt Daniel D   Rodon Jordi J   Landolfi Stefania S   Prat Aleix A   Espín Eloy E   Charco Ramón R   Nuciforo Paolo P   Vivancos Ana A   Shao Wenlin W   Tabernero Josep J   Palmer Héctor G HG  

Clinical cancer research : an official journal of the American Association for Cancer Research 20150729 3

<h4>Purpose</h4>Oncogenic mutations in the KRAS/PI3K/AKT pathway are one of the most frequent alterations in cancer. Although PI3K or AKT inhibitors show promising results in clinical trials, drug resistance frequently emerges. We previously revealed Wnt/β-catenin signaling hyperactivation as responsible for such resistance in colorectal cancer. Here we investigate Wnt-mediated resistance in patients treated with PI3K or AKT inhibitors in clinical trials and evaluate the efficacy of a new Wnt/ta  ...[more]

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