针对癌症治疗的 PI3K 通路。
Targeting the PI3K pathway for cancer therapy.
机构信息
Division of Hematology & Oncology, Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Future Med Chem. 2012 Jun;4(9):1153-69. doi: 10.4155/fmc.12.56.
Abstract
The PI3K pathway plays an important role in key cellular functions such as cell growth, proliferation and survival. Genetic and epigenetic alterations in different pathway components lead to aberrant pathway activation and have been observed in high frequencies in various tumor types. Consequently, significant effort has been made to develop antineoplastic agents targeting different nodes in this pathway. Additionally, PI3K pathway status may have predictive and prognostic implications, and may contribute to drug resistance in tumor cells. This article provides an overview of our current knowledge of the PI3K pathway with an emphasis on its application in cancer treatment.
摘要
PI3K 通路在细胞的重要功能中发挥着重要作用，如细胞生长、增殖和存活。不同通路成分的遗传和表观遗传改变导致异常通路激活，并在各种肿瘤类型中高频观察到。因此，人们做出了巨大努力来开发针对该通路不同节点的抗肿瘤药物。此外，PI3K 通路状态可能具有预测和预后意义，并可能导致肿瘤细胞的耐药性。本文概述了我们目前对 PI3K 通路的认识，重点介绍其在癌症治疗中的应用。
相似文献
1
Targeting the PI3K pathway for cancer therapy.
Future Med Chem. 2012 Jun;4(9):1153-69. doi: 10.4155/fmc.12.56.
2
Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.
Int J Mol Sci. 2024 Feb 6;25(4):1973. doi: 10.3390/ijms25041973.
3
The PI3K pathway as drug target in human cancer.
J Clin Oncol. 2010 Feb 20;28(6):1075-83. doi: 10.1200/JCO.2009.25.3641. Epub 2010 Jan 19.
4
Receptor tyrosine kinases in PI3K signaling: The therapeutic targets in cancer.
Semin Cancer Biol. 2019 Dec;59:3-22. doi: 10.1016/j.semcancer.2019.03.006. Epub 2019 Mar 31.
5
Targeting PI3K/Akt signal transduction for cancer therapy.
Signal Transduct Target Ther. 2021 Dec 16;6(1):425. doi: 10.1038/s41392-021-00828-5.
6
Status of PI3K inhibition and biomarker development in cancer therapeutics.
Ann Oncol. 2010 Apr;21(4):683-691. doi: 10.1093/annonc/mdp347. Epub 2009 Aug 27.
7
Phosphoinositide 3'-kinase inhibition in chronic lymphocytic leukemia.
Hematol Oncol Clin North Am. 2013 Apr;27(2):329-39. doi: 10.1016/j.hoc.2012.12.002.
8
Targeting the PI3K signaling pathway in cancer therapy.
Expert Opin Ther Targets. 2012 Jan;16(1):121-30. doi: 10.1517/14728222.2011.644788. Epub 2012 Jan 12.
9
Targeting the PI3K/AKT/mTOR signaling axis in children with hematologic malignancies.
Paediatr Drugs. 2012 Oct 1;14(5):299-316. doi: 10.2165/11594740-000000000-00000.
10
GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway.
Mol Cancer Ther. 2011 Dec;10(12):2426-36. doi: 10.1158/1535-7163.MCT-11-0446. Epub 2011 Oct 13.
引用本文的文献
1
The Role of RAC2 and PTTG1 in Cancer Biology.
Cells. 2025 Feb 23;14(5):330. doi: 10.3390/cells14050330.
2
Insilco and Invitro approaches identify novel dual PI3K/AKT pathway inhibitors to control acute myeloid leukemia cell proliferations.
Med Oncol. 2022 Oct 8;39(12):249. doi: 10.1007/s12032-022-01846-1.
3
Mechanisms of Natural Extracts of That Target Lipid-Dependent Cancer Pathways: A View from the Signaling Pathway.
Int J Mol Sci. 2022 May 26;23(11):5972. doi: 10.3390/ijms23115972.
4
Genetic Polymorphisms in microRNA Genes Targeting PI3K/Akt Signal Pathway Modulate Cervical Cancer Susceptibility in a Chinese Population.
Front Genet. 2022 Apr 14;13:856505. doi: 10.3389/fgene.2022.856505. eCollection 2022.
5
The Expression of Signaling Genes in Breast Cancer Cells.
Biology (Basel). 2022 Apr 3;11(4):555. doi: 10.3390/biology11040555.
6
A doxorubicin-platinum conjugate system: impacts on PI3K/AKT actuation and apoptosis in breast cancer cells.
RSC Adv. 2021 Jan 25;11(8):4818-4828. doi: 10.1039/d0ra06708c. eCollection 2021 Jan 21.
7
Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway.
Int J Biol Sci. 2022 Mar 14;18(6):2419-2438. doi: 10.7150/ijbs.67200. eCollection 2022.
8
The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers.
Am J Cancer Res. 2021 Dec 15;11(12):5833-5855. eCollection 2021.
9
Cell-Penetrating Peptide-Modified Graphene Oxide Nanoparticles Loaded with Rictor siRNA for the Treatment of Triple-Negative Breast Cancer.
Drug Des Devel Ther. 2021 Dec 10;15:4961-4972. doi: 10.2147/DDDT.S330059. eCollection 2021.
10
Pathway-extended gene expression signatures integrate novel biomarkers that improve predictions of patient responses to kinase inhibitors.
MedComm (2020). 2020 Dec 10;1(3):311-327. doi: 10.1002/mco2.46. eCollection 2020 Dec.
本文引用的文献
1
Disruption of the AKT pathway inhibits metastasis in an orthotopic model of head and neck squamous cell carcinoma.
Laryngoscope. 2011 Nov;121(11):2359-65. doi: 10.1002/lary.22180.
2
p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors.
Oncogene. 2012 Jul 5;31(27):3277-86. doi: 10.1038/onc.2011.492. Epub 2011 Oct 24.
3
PIK3CA kinase domain mutation identifies a subgroup of stage III colon cancer patients with poor prognosis.
Cell Oncol (Dordr). 2011 Dec;34(6):523-31. doi: 10.1007/s13402-011-0054-4. Epub 2011 Aug 10.
4
Ridaforolimus: a promising drug in the treatment of soft-tissue sarcoma and other malignancies.
Future Oncol. 2011 Jul;7(7):827-39. doi: 10.2217/fon.11.57.
5
PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib.
BMC Cancer. 2011 Jun 15;11:248. doi: 10.1186/1471-2407-11-248.
6
Molecular mechanism of HIF-1-independent VEGF expression in a hepatocellular carcinoma cell line.
Int J Mol Med. 2011 Sep;28(3):449-54. doi: 10.3892/ijmm.2011.719. Epub 2011 Jun 8.
7
Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification.
Blood. 2011 Aug 4;118(5):1264-73. doi: 10.1182/blood-2011-01-328567. Epub 2011 Jun 7.
8
INPP4B: the new kid on the PI3K block.
Oncotarget. 2011 Apr;2(4):321-8. doi: 10.18632/oncotarget.260.
9
PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer.
Cancer Res. 2011 Jun 15;71(12):4061-7. doi: 10.1158/0008-5472.CAN-11-0549. Epub 2011 Apr 8.
10
mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.
Cancer Res. 2011 May 1;71(9):3246-56. doi: 10.1158/0008-5472.CAN-10-4058. Epub 2011 Mar 23.
Zotero 插件