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Erratum: Mapelli, S.N., et al. A Novel Prostate Cell Type-Specific Gene Signature to Interrogate Prostate Tumor Differentiation Status and Monitor Therapeutic Response (Running Title: Phenotypic Classification of Prostate Tumors). Cancers 2020, 12, 176
Open AccessReview

Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress

by 1, 2,3,* and 1,*
1
Department of Pathology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
2
Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria
3
Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(10), 2972; https://doi.org/10.3390/cancers12102972
Received: 6 September 2020 / Revised: 3 October 2020 / Accepted: 12 October 2020 / Published: 14 October 2020
Most gastrointestinal stromal tumors (GISTs) arise due to gain-of-function mutations of KIT and PDGFRA, encoding the receptor tyrosine kinase (RTK). The introduction of the RTK inhibitor imatinib has significantly improved the management of GISTs; however, drug resistance remains a challenge. Constitutive autophosphorylation of RTKs is associated with the activation of the PI3K/AKT/mTOR pathway. Especially, this pathway plays a pivotal role in mRNA translation initiation, directly regulated by eukaryotic initiation factors (eIFs). This review highlights the progress for targeting PI3K/AKT/mTOR-dependent mechanisms in GISTs and explores the relationship between mTOR downstream eIFs and the development of GISTs, which may be a promising future therapeutic target for this tumor entity.
Gastrointestinal stromal tumor (GIST) originates from interstitial cells of Cajal (ICCs) in the myenteric plexus of the gastrointestinal tract. Most GISTs arise due to mutations of KIT and PDGFRA gene activation, encoding the receptor tyrosine kinase (RTK). The clinical use of the RTK inhibitor imatinib has significantly improved the management of GIST patients; however, imatinib resistance remains a challenge. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a critical survival pathway for cell proliferation, apoptosis, autophagy and translation in neoplasms. Constitutive autophosphorylation of RTKs has an impact on the activation of the PI3K/AKT/mTOR pathway. In several preclinical and early-stage clinical trials PI3K/AKT/mTOR signaling inhibition has been considered as a promising targeted therapy strategy for GISTs. Various inhibitory drugs targeting different parts of the PI3K/AKT/mTOR pathway are currently being investigated in phase Ι and phase ΙΙ clinical trials. This review highlights the progress for PI3K/AKT/mTOR-dependent mechanisms in GISTs, and explores the relationship between mTOR downstream signals, in particular, eukaryotic initiation factors (eIFs) and the development of GISTs, which may be instrumental for identifying novel therapeutic targets. View Full-Text
Keywords: gastrointestinal stromal tumors; PI3K/AKT/mTOR; inhibitor; eIFs gastrointestinal stromal tumors; PI3K/AKT/mTOR; inhibitor; eIFs
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MDPI and ACS Style

Duan, Y.; Haybaeck, J.; Yang, Z. Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress. Cancers 2020, 12, 2972. https://doi.org/10.3390/cancers12102972

AMA Style

Duan Y, Haybaeck J, Yang Z. Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress. Cancers. 2020; 12(10):2972. https://doi.org/10.3390/cancers12102972

Chicago/Turabian Style

Duan, Yi; Haybaeck, Johannes; Yang, Zhihui. 2020. "Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress" Cancers 12, no. 10: 2972. https://doi.org/10.3390/cancers12102972

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