2026-04-29T06:16:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/272162026-02-10T01:18:35Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud
author
Montero-Conde, Cristina
author
Ruiz-Llorente, Sergio
author
Dominguez, Jose M
author
Knauf, Jeffrey A
author
Viale, Agnes
author
Sherman, Eric J
author
Ryder, Mabel
author
Ghossein, Ronald A
author
Rosen, Neal
author
Fagin, James A
2026-02-09T08:56:42Z
2026-02-09T08:56:42Z
2013-05
Cancer Discov . 2013 May;3(5):520-33.
https://hdl.handle.net/20.500.12105/27216
23365119
The RAF inhibitor vemurafenib (PLX4032) increases survival in patients with BRAF-mutant metastatic melanoma, but has limited efficacy in patients with colorectal cancers. Thyroid cancer cells are also comparatively refractory to RAF inhibitors. In contrast to melanomas, inhibition of mitogen-activated protein kinase (MAPK) signaling by PLX4032 is transient in thyroid and colorectal cancer cells. The rebound in extracellular signal-regulated kinase (ERK) in thyroid cells is accompanied by increased HER3 signaling caused by induction of ERBB3 (HER3) transcription through decreased promoter occupancy by the transcriptional repressors C-terminal binding protein 1 and 2 and by autocrine secretion of neuregulin-1 (NRG1). The HER kinase inhibitor lapatinib prevents MAPK rebound and sensitizes BRAF-mutant thyroid cancer cells to RAF or MAP-ERK kinase inhibitors. This provides a rationale for combining ERK pathway antagonists with inhibitors of feedback-reactivated HER signaling in this disease. The determinants of primary resistance to MAPK inhibitors vary between cancer types, due to preferential upregulation of specific receptor tyrosine kinases, and the abundance of their respective ligands.
eng
Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas.
research article
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URL
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40d386b3aed49d1fedb6d04cd1354045
3481651
application/pdf
reliefoffeedbackinhibition_2013.pdf