The protein tyrosine phosphatase family (PTP) contains a group of 
dual-specificity phosphatases (DUSPs) that regulate the activivity of MAP 
kinases (MAPKs), which are key effectors in the control of cell growth and 
survival in physiological and pathological processes, including cancer. These 
phosphatases, named as MKP-DUSPs, include the MAPK phosphatases (MKPs) as well 
as a group of small-size atypical DUSPs structurally and functionally related to 
the MKPs. MKP-DUSPs, in most of the cases, are direct inactivators of MAPKs by 
dephosphorylation of both the Thr and the Tyr regulatory residues at the MAPKs 
catalytic loop. In some other cases, MKP-DUSPs regulate the activity of MAPKs 
indirectly, acting through upstream MAPK pathways components. The active 
involvement of MKP-DUSPs in oncogenesis or resistance to cancer therapies is now 
well documented, making the search and validation of MKP-DUSPs inhibitors a 
prominent area in clinical cancer research. Here, we review the current 
knowledge on the role of MKP-DUSPs in human cancer, the status of the 
preclinical development and validation of specific MKP-DUSP inhibitors, and the 
potential of MKP-DUSPs as targets for anti-cancer drugs.