Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer
Pappalardo, Francesco; Russo, Giulia; Candido, Saverio; Pennisi, Marzio; Cavalieri, Salvatore; Motta, Santo; McCubrey, James A.; Nicoletti, Ferdinando; Libra, Massimo
Background Malignant melanoma is an aggressive tumor of the skin and seems to be resistant to current therapeutic approaches. Melanocytic transformation is thought to occur by sequential accumulation of genetic and molecular alterations able to activate the Ras/Raf/MEK/ERK (MAPK) and/or the PI3K/AKT (AKT) signalling pathways. Specifically, mutations of B-RAF activate MAPK pathway resulting in cell cycle progression and apoptosis prevention. According to these findings, MAPK and AKT pathways may represent promising therapeutic targets for an otherwise devastating disease. Result Here we show a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. Overall, this computational approach may accelerate the drug discovery process and encourages the identification of novel pathway activators with consequent development of novel antioncogenic compounds to overcome tumor cell resistance to conventional therapeutic agents. The source code of the various versions of the model are available as S1 Archive.
Pappalardo, Francesco, & Russo, Giulia, & Candido, Saverio, & Pennisi, Marzio, & Cavalieri, Salvatore, & Motta, Santo, & McCubrey, James A., & Nicoletti, Ferdinando, & Libra, Massimo. (March 2016). Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer. PLoS ONE, 11(3), 1- 10. Retrieved from http://hdl.handle.net/10342/5664
Pappalardo, Francesco, and Russo, Giulia, and Candido, Saverio, and Pennisi, Marzio, and Cavalieri, Salvatore, and Motta, Santo, and McCubrey, James A., and Nicoletti, Ferdinando, and Libra, Massimo. "Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer". PLoS ONE. 11:3. (1-10), March 2016. October 17, 2018. http://hdl.handle.net/10342/5664.
Pappalardo, Francesco and Russo, Giulia and Candido, Saverio and Pennisi, Marzio and Cavalieri, Salvatore and Motta, Santo and McCubrey, James A. and Nicoletti, Ferdinando and Libra, Massimo, "Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer," PLoS ONE 11, no. 3 (March 2016), http://hdl.handle.net/10342/5664 (accessed October 17, 2018).
Pappalardo, Francesco, Russo, Giulia, Candido, Saverio, Pennisi, Marzio, Cavalieri, Salvatore, Motta, Santo, McCubrey, James A., Nicoletti, Ferdinando, Libra, Massimo. Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer. PLoS ONE. March 2016; 11(3): 1-10. http://hdl.handle.net/10342/5664. Accessed October 17, 2018.