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Citations to this article

Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3
Ethan V. Abel, … , Paolo Fortina, Andrew E. Aplin
Ethan V. Abel, … , Paolo Fortina, Andrew E. Aplin
Published April 1, 2013
Citation Information: J Clin Invest. 2013;123(5):2155-2168. https://doi.org/10.1172/JCI65780.
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Research Article Oncology Article has an altmetric score of 15

Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3

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Abstract

The mechanisms underlying adaptive resistance of melanoma to targeted therapies remain unclear. By combining ChIP sequencing with microarray-based gene profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription factor that promotes resistance to RAF inhibitors in melanoma. Enhanced ERBB3 signaling promoted resistance to RAF pathway inhibitors in cultured melanoma cell lines and in mouse xenograft models. ERBB3 signaling was dependent on ERBB2; targeting ERBB2 with lapatinib in combination with the RAF inhibitor PLX4720 reduced tumor burden and extended latency of tumor regrowth in vivo versus PLX4720 alone. These results suggest that enhanced ERBB3 signaling may serve as a mechanism of adaptive resistance to RAF and MEK inhibitors in melanoma and that cotargeting this pathway may enhance the clinical efficacy and extend the therapeutic duration of RAF inhibitors.

Authors

Ethan V. Abel, Kevin J. Basile, Curtis H. Kugel III, Agnieszka K. Witkiewicz, Kaitlyn Le, Ravi K. Amaravadi, Giorgos C. Karakousis, Xiaowei Xu, Wei Xu, Lynn M. Schuchter, Jason B. Lee, Adam Ertel, Paolo Fortina, Andrew E. Aplin

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 Total
Citations: 2 2 8 16 12 12 9 17 12 16 27 23 6 162
Citation information
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Citations to this article in year 2017 (12)

Title and authors Publication Year
Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas In Vivo and Ex Vivo
EJ Hartsough, CH Kugel, MJ Vido, AC Berger, TJ Purwin, A Goldberg, MA Davies, MJ Schiewer, KE Knudsen, G Bollag, AE Aplin
Molecular cancer therapeutics 2017
The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition
V Thakur, J Lu, G Roscilli, L Aurisicchio, M Cappelletti, E Pavoni, WL White, B Bedogni
Oncotarget 2017
Resistance mechanisms to genetic suppression of mutant NRAS in melanoma:
JP Robinson, VW Rebecca, DA Kircher, MR Silvis, I Smalley, GT Gibney, KJ Lastwika, G Chen, MA Davies, D Grossman, KS Smalley, SL Holmen, MW VanBrocklin
Melanoma Research 2017
Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas
CM Beltrami, MB Reis, MC Barros-Filho, FA Marchi, H Kuasne, CA Pinto, S Ambatipudi, Z Herceg, LP Kowalski, SR Rogatto
Clinical Epigenetics 2017
Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma
J Wouters, M Vizoso, A Martinez-Cardus, FJ Carmona, O Govaere, T Laguna, J Joseph, P Dynoodt, C Aura, M Foth, R Cloots, K Hurk, B Balint, IG Murphy, EW McDermott, K Sheahan, K Jirström, B Nodin, G Mallya-Udupi, JJ van Oord, WM Gallagher, M Esteller
BMC Medicine 2017
ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
D Alvarado, GF Ligon, JS Lillquist, SB Seibel, G Wallweber, VM Neumeister, DL Rimm, G McMahon, TM LaVallee, N Cordes
PloS one 2017
Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma
B Eskiocak, EA McMillan, S Mendiratta, RK Kollipara, H Zhang, CG Humphries, C Wang, J Garcia-Rodriguez, M Ding, A Zaman, TI Rosales, U Eskiocak, MP Smith, J Sudderth, K Komurov, RJ Deberardinis, C Wellbrock, MA Davies, JA Wargo, Y Yu, JK de Brabander, NS Williams, L Chin, H Rizos, GV Long, R Kittler, MA White
Cancer Discovery 2017
FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway
K Li, Q Guo, J Yang, H Chen, K Hu, J Zhao, X Pang, S Zhou, Y Dang, L Li
Oncotarget 2017
Overcoming resistance to BRAF inhibitors
I Arozarena, C Wellbrock
Annals of translational medicine 2017
Enhanced response of melanoma cells to MEK inhibitors following unbiased IGF-1R down-regulation
N Suleymanova, C Crudden, C Worrall, A Dricu, A Girnita, L Girnita
Oncotarget 2017
FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer
S Sarkar, MR O'Connell, Y Okugawa, BS Lee, Y Toiyama, M Kusunoki, RD Daboval, A Goel, P Singh
Molecular cancer research : MCR 2017
Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state.
Fallahi-Sichani M, Becker V, Izar B, Baker GJ, Lin JR, Boswell SA, Shah P, Rotem A, Garraway LA, Sorger PK
Molecular Systems Biology 2017

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