Although PI3K/AKT has undoubtedly been one of the most important pathways that impact tumorigenesis and proliferation, PI3K-beta has not been considered as a stand-alone target for potential cancer treatment until the...Although PI3K/AKT has undoubtedly been one of the most important pathways that impact tumorigenesis and proliferation, PI3K-beta has not been considered as a stand-alone target for potential cancer treatment until the re-cent discovery of the key role that PI3K-beta plays in phosphatase and TENsin homolog （PTEN）-deficient tumors. Medicinal chemistry efforts from the pharmaceutical industry and academia in the past few years have led to sig-nificant advancements in understanding beta isoform selectivity and in the development of a clinical drug candidate.展开更多
In gliomas, the canonical Wingless/Int（WNT）/b-catenin pathway is increased while peroxisome proliferator-activated receptor gamma（PPAR-c） is downregulated.The two systems act in an opposite manner. This review foc...In gliomas, the canonical Wingless/Int（WNT）/b-catenin pathway is increased while peroxisome proliferator-activated receptor gamma（PPAR-c） is downregulated.The two systems act in an opposite manner. This review focuses on the interplay between WNT/b-catenin signaling and PPAR-c and their metabolic implications as potential therapeutic target in gliomas. Activation of the WNT/bcatenin pathway stimulates the transcription of genes involved in proliferation, invasion, nucleotide synthesis,tumor growth, and angiogenesis. Activation of PPAR-c agonists inhibits various signaling pathways such as the JAK/STAT, WNT/b-catenin, and PI3 K/Akt pathways,which reduces tumor growth, cell proliferation, cell invasiveness, and angiogenesis. Nonsteroidal anti-inflammatory drugs, curcumin, antipsychotic drugs, adiponectin,and sulforaphane downregulate the WNT/b-catenin pathway through the upregulation of PPAR-c and thus appear to provide an interesting therapeutic approach for gliomas.Temozolomide（TMZ） is an antiangiogenic agent. The downstream action of this opposite interplay may explain the TMZ-resistance often reported in gliomas.展开更多
文摘Although PI3K/AKT has undoubtedly been one of the most important pathways that impact tumorigenesis and proliferation, PI3K-beta has not been considered as a stand-alone target for potential cancer treatment until the re-cent discovery of the key role that PI3K-beta plays in phosphatase and TENsin homolog （PTEN）-deficient tumors. Medicinal chemistry efforts from the pharmaceutical industry and academia in the past few years have led to sig-nificant advancements in understanding beta isoform selectivity and in the development of a clinical drug candidate.
文摘In gliomas, the canonical Wingless/Int（WNT）/b-catenin pathway is increased while peroxisome proliferator-activated receptor gamma（PPAR-c） is downregulated.The two systems act in an opposite manner. This review focuses on the interplay between WNT/b-catenin signaling and PPAR-c and their metabolic implications as potential therapeutic target in gliomas. Activation of the WNT/bcatenin pathway stimulates the transcription of genes involved in proliferation, invasion, nucleotide synthesis,tumor growth, and angiogenesis. Activation of PPAR-c agonists inhibits various signaling pathways such as the JAK/STAT, WNT/b-catenin, and PI3 K/Akt pathways,which reduces tumor growth, cell proliferation, cell invasiveness, and angiogenesis. Nonsteroidal anti-inflammatory drugs, curcumin, antipsychotic drugs, adiponectin,and sulforaphane downregulate the WNT/b-catenin pathway through the upregulation of PPAR-c and thus appear to provide an interesting therapeutic approach for gliomas.Temozolomide（TMZ） is an antiangiogenic agent. The downstream action of this opposite interplay may explain the TMZ-resistance often reported in gliomas.
