In this example we use gene expression data from a BRCA cancer sample (TCGA data, sample id TCGA.BH.A1FM - example data).

You can download the example file from here.

Sorafenib is a multiple kinase inhibitor used in clinical for the treatment of several cancers mainly by its activity as angiogenesis inhibitor, due its action in VEGFR and PDGFR proteins. Using PathAct we simulate In Silico treatment with sorafenib in one TCGA breast cancer sample. So, we select sorafenib in the drug search panel and update the pathways. It may expend some minutes to show the results.

We show how there are some pathways altered as consequence of drug addition (several targets, highlighted in green) and most of those pathways are down-regulated (inhibitor).

The main therapeutic action of sorafenib is its effect as angiogenesis suppressor and we expect see those effect in our In Silico prediction. VEGF signaling pathway is one the canonical angiogenesis pathways and we observe how most of their circuits are down-regulated and functions like “Angiogenesis” or “Cell adhesion” are directly repressed.

Moreover, VEGF signaling pathway is not the only therapeutic related pathway, and PathAct shows similar In Silico effects in others pathways like HIF-1 signaling pathway (FLT1 circuit) or Focal adhesion pathway.

Acting as multiple kinase inhibitor, sorafenib binds to others proteins like MAPK proteins, limiting the tumor growth and inducing apoptosis. In our model, we show how some pathways like RAP-1 or Sphingolipid signaling pathways provokes changes in cell cycle and growth and many others pathways alter transcription regulation, whose functional effect is tissue dependent.