The advantages of pathway intersections analysis include revealing whether different cancers have same chemoresis tant mechanisms, and determining whether some common genes involved in these chemoresistant mechanisms. As expected, we observed a great deal of correspondence between the response interactions of ovarian and lung cancer expression data by intersecting pathways. The ana lysis of platinum based chemotherapeutic agents revealed insights into common responses among the chemoresistant mechanisms as well as the candidate genes such as Bcl 2, AHR and, most importantly, SOD1. The results also indi cate that the WNT signaling pathway, the Notch signaling pathway and the FAK pathway are involved in ovarian and lung chemoresistance.

Therefore, further analysis of our computational experiment results may reveal additional chemoresistance mechanisms, which indicates this approach can anticipate target identification and chemore sistance in the future development of cancer drugs. Pathways with a dissimilar response to that of known modes of biological action can be easily identified early in the drug development process to avert repeated and costly clinical trails. This approach reveals chemoresis tance associated pathways in scilicon and enables easier comparisons with the generated graphs. Furthermore, by exploring signature genes involved in chemoresistance mechanisms, this approach sheds light on how these genes or pathways interact with each other, and provides analysis of the betweenness centrality and degree values of genes in pathways.

In summary, this method is suffi ciently flexible to accommodate various types of biologi cal network information and experimental data, and offers not only insights into the mechanisms of chemore sistance but also provides information on potential candi date target genes for future drug development efforts. Introduction Receptor tyrosine kinases consist of a large family of receptors whose members serve a wide range of physiological functions including growth, differentia tion and synaptic modulation. The members of this receptor family generally feature an extracellular ligand binding domain, linked by a transmembrane domain to an intracellular tyrosine kinase domain, as well as sev eral SH2 domain binding sites.

It is generally believed that the mechanism of RTK signaling involves Batimastat ligand induced dimerization of the RTK followed by cross phosphorylation of the tyrosine containing motifs, which subsequently interact with SH2 domain containing molecules such as the PI3 kinase, PLC g, Src, SHP 2, Grb 2 and RasGAP, to effect downstream responses. The large family of G protein coupled receptors activates heterotrimeric G proteins and can mediate several cellular processes, including prolifera tion, differentiation and survival. The ERK1/2 signaling pathway is among the major effector pathways through which GPCRs mediate their responses.