Résumé
Transforming growth factor beta (TGF-beta) is an important signaling molecule which is expressed in three different isoforms in mammals (i.e. TGF-beta 1, -beta 2, and -beta 3). The interaction between TGF-beta and its receptor triggers several pathways, which are classified into SMAD-dependent (canonical) and SMAD-independent (non-canonical) signaling, whose activation/transduction is finely regulated by several mechanisms. TGF-beta is involved in many physiological and pathological processes, assuming a dualistic role in cancer progression depending on tumor stage. Indeed, TGF-beta inhibits cell proliferation in early-stage tumor cells, while it promotes cancer progression and invasion in advanced tumors, where high levels of TGF-beta have been reported in both tumor and stromal cells. In particular, TGF-beta signaling has been found to be strongly activated in cancers after treatment with chemotherapeutic agents and radiotherapy, resulting in the onset of drug resistance conditions. In this review we provide an up-to-date description of several mechanisms involved in TGF-beta-mediated drug resistance, and we report different strategies that are currently under development in order to target TGF-beta pathway and increase tumor sensitivity to therapy.