Abstract: Metabolomics has become a rising field of research
for various diseases, particularly cancer. Increases or decreases in
metabolite concentrations in the human body are indicative of various
cancers. Further elucidation of metabolic pathways and their
significance in cancer research may greatly spur medicinal discovery.
We analyzed the metabolomics profiles of lung cancer. Thirty-three
metabolites were selected as significant. These metabolites are
involved in 37 metabolic pathways delivered by MetaboAnalyst
software. The top pathways are glyoxylate and dicarboxylate
pathway (its hubs are formic acid and glyoxylic acid) along with
Citrate cycle pathway followed by Taurine and hypotaurine pathway
(the hubs in the latter are taurine and sulfoacetaldehyde) and Glycine,
serine, and threonine pathway (the hubs are glycine and L-serine). We
studied interactions of the metabolites with the proteins involved in
cancer-related signaling networks, and developed an approach to
metabolomics biomarker use in cancer diagnostics. Our analysis
showed that a significant part of lung-cancer-related metabolites
interacts with main cancer-related signaling pathways present in this
network: PI3K–mTOR–AKT pathway, RAS–RAF–ERK1/2 pathway,
and NFKB pathway. These results can be employed for use of
metabolomics profiles in elucidation of the related cancer proteins
signaling networks.
Abstract: NFκB activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFa) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are no any quantitative or qualitative results of comparison assessment on inhibition effect between different single drugs or drug combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific single drugs and drug combinations on the NFκB pathway in MM, especially the prediction of synergistic drug combinations.