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PAX3-FOXO1: Zooming in on an "undruggable" target


Wachtel, Marco; Schäfer, Beat W (2018). PAX3-FOXO1: Zooming in on an "undruggable" target. Seminars in Cancer Biology, 50:115-123.

Abstract

Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general.

Abstract

Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2018
Deposited On:08 Feb 2018 12:12
Last Modified:19 Aug 2018 13:55
Publisher:Elsevier
ISSN:1044-579X
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.semcancer.2017.11.006
PubMed ID:29146205
Project Information:
  • : FunderSNSF
  • : Grant ID310030_156923
  • : Project TitleTowards a specific therapy for rhabdoymosarcoma: approaches to target PAX3/FOXO1 and the cancer stem cell compartment
  • : FunderSNSF
  • : Grant ID31003A_138460
  • : Project TitleMolecular mechanisms underlying the pathogenesis of rhabdomyosarcoma

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