Journal ArticleDOI
The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches.
TLDR
A large-scale characterization of the cancer genome might offer personalized cancer genomic information, which may improve the anti-tumor efficacy of signalling inhibitors.Abstract:
Introduction: The RAS/RAF/MAP kinase–ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) (MAPK) and the PI3K/AKT/mammalian target of rapamycin (mTOR) (PI3K) pathways are frequently deregulated in human cancer as a result of genetic alterations in their components or upstream activation of cell-surface receptors. These signalling cascades are regulated by complex feedback and cross-talk mechanisms. Areas covered: In this review the key components of the MAPK and AKT pathways and their molecular alterations are described. The complex interactions between these signalling cascades are also analysed. Expert opinion: The observation that the MAPK and the PI3K pathways are often deregulated in human cancer makes the components of these signalling cascades interesting targets for therapeutic intervention. Recently, the presence of compensatory loops that activate one pathway following the blockade of the other signalling cascade has been demonstrated. Therefore, the blockade of both pathways with combin...read more
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Journal ArticleDOI
The MAPK pathway across different malignancies: a new perspective.
TL;DR: Understanding the differential nature of activation of the MAPK/ERK pathway in each tumor type is critical in developing single and combination regimens, because different tumors have unique mechanisms of primary and secondary signaling and subsequent sensitivity to drugs.
Journal ArticleDOI
Landscape of genomic alterations in cervical carcinomas
Akinyemi I. Ojesina,Lee Lichtenstein,Samuel S. Freeman,Chandra Sekhar Pedamallu,Ivan Imaz-Rosshandler,Trevor J. Pugh,Andrew D. Cherniack,Lauren Ambrogio,Kristian Cibulskis,Bjørn Enge Bertelsen,Sandra Romero-Cordoba,Victor Trevino,Karla Vazquez-Santillan,Alberto Salido Guadarrama,Alexi A. Wright,Mara Rosenberg,Fujiko Duke,Bethany Kaplan,Rui Wang,Elizabeth Nickerson,Heather M. Walline,Michael S. Lawrence,Chip Stewart,Scott L. Carter,Aaron McKenna,Iram P. Rodriguez-Sanchez,Magali Espinosa-Castilla,Kathrine Woie,Line Bjørge,Elisabeth Wik,Mari K. Halle,Erling A. Hoivik,Camilla Krakstad,Nayeli Belem Gabiño,Gabriela Sofía Gómez-Macías,Lezmes D. Valdez-Chapa,María Lourdes Garza-Rodríguez,German Maytorena,Jorge Vazquez,Carlos Rodea,Adrian Cravioto,Maria L. Cortes,Heidi Greulich,Christopher P. Crum,Donna Neuberg,Alfredo Hidalgo-Miranda,Claudia Rangel Escareno,Lars A. Akslen,Thomas E. Carey,Olav Karsten Vintermyr,Stacey Gabriel,Hugo A. Barrera-Saldaña,Jorge Melendez-Zajgla,Gad Getz,Helga B. Salvesen,Matthew Meyerson +55 more
TL;DR: Several recurrent genomic alterations in cervical carcinomas are demonstrated that suggest new strategies to combat this disease.
Journal ArticleDOI
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer—Response
Mario Sznol,Lieping Chen +1 more
TL;DR: Several key challenges remain to optimize development of PD-1/B7-H1 pathway blockade, including defining the biologic significance of all potential ligand–receptor interactions in the tumor microenvironment, developing more accurate predictive biomarkers of response, determining the breadth of activity in human malignancies, and developing rational combinations of therapy.
Journal ArticleDOI
The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer
TL;DR: This review addresses the oncopharmacological properties of curcumin at the molecular level, whereby the phenotypical/biological changes induced in cancer cells upon completion of theCurcumin-triggered signaling cascade(s) are addressed in the framework of the hallmarks of cancer.
Journal ArticleDOI
Molecular aspects of cancer cell resistance to chemotherapy
Magali Rebucci,Carine Michiels +1 more
TL;DR: The stemness properties of a few cancer cells as well as components of the tumor stroma, like fibroblasts and tumor-associated macrophages but also hypoxia, also help tumor to resist to anticancer agents.
References
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Comprehensive genomic characterization defines human glioblastoma genes and core pathways
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TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
Journal ArticleDOI
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Anne Brunet,Azad Bonni,Michael J. Zigmond,Michael Z. Lin,Peter Juo,Linda Hu,Michael J. Anderson,Karen C. Arden,John Blenis,Michael E. Greenberg +9 more
TL;DR: It is demonstrated that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors, which triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.
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