Osteopontin (OPN) is a matricellular phosphoglycoprotein overexpressed in several tumor types and can activate several aspects of cancer progression in solid and non‑solid tumors. In the present review, the roles of OPN in mediating resistance to chemotherapy and radiotherapy and their main associated signaling pathways were summarized and discussed. Furthermore, it was detailed how OPN expression may be able to modulate resistance to these therapies by controlling epithelial cell plasticity, stemness potential and cell survival. Based on these data, the use of OPN and associated signaling was then proposed as potential molecular targets in order to sensitize resistant cells to main current therapeutic approaches. Finally, based on experimental evidence obtained by our group, the importance of investigating the specific roles OPN splicing isoforms have and how their properties may specifically control resistance to therapy was highlighted. These data elucidate a better understanding of how total OPN and their splicing isoforms, as well as their associated signaling, may contribute to main aspects of chemoresistance and radioresistance, such as those controlling cell survival, apoptosis, autophagy, stemness, epithelial cell plasticity and associated cell receptors.
Keywords: osteopontin; chemoresistance; radioresistance; splicing isoforms; signaling pathways.