Since over 20 years, novel therapies targeting intra- and extra-cellular signaling are developed.These therapies annihilate major oncogenic pathways, that drive tumorigenesis in each cancer sub-types. The most recent & spectacular example is represented by a mutated B-Raf inhibitor (Vemurafenib) with which, under treatment, partial and complete remissions were observed in metastatic melanoma patients. Compounds inhibiting PI3K signalling pathway are also under clinical trials, with a compound targeting PI3Kδ GS-1101 (Idelalisib/CAL-101) in immune compartment, being the first PI3K inhibitor to be approved for clinical use. These therapies, however, rapidly induce resistance.
These responses to treatment come from cancer and metastatic cells themselves, but also from the tumor in its microenvironment. Understanding molecular mechanisms underpinning interconnection of oncogenic cellular signalling and cellular metabolism or genomic instability, as well as understanding common signalling pathways in immune, cancer and vascular cells will help us to predict resistance to these signal-targeted therapies and to imagine the future anti-cancer treatments.