Jornal de Biomarcadores Moleculares e Diagnóstico

CIP2A as a Potential Stratification Marker and Target for Tumor Responsiveness to DNA Damaging Therapies

Abstract

Johannes Routila and Jukka Westermarck

DNA damaging therapies such as irradiation therapy and chemotherapy are used in the treatment of numerous cancer types both definitively and in combination with surgery. However, many cancer types show intrinsic resistance to DNA damaging therapies resulting in failure in tumor eradication and relapse after therapy. Thus it would be very useful to identify novel diagnostic strategies to predict for tumor radio tolerance. Head and neck squamous cell carcinoma (HNSCC) is a common cancer type characterized with great heterogeneity and lack of predictive markers for tumor radio resistance. Recent literature has revealed Cancerous inhibitor of PP2A, CIP2A, as a novel potential diagnostic marker for HNSCC, and other tumors, that show high radio resistance. In particular, we recently identified a functional link between stem cell factor Oct4 and CIP2A in HNSCC cells and demonstrated their potential role in predicting for HNSCC tumor response to radiotherapy. CIP2A´s role in mediating radio resistance in vivo has also been recently confirmed by using genetic mouse model. This raises an interesting possibility that diagnostic evaluation of CIP2A in combination with other factors indicative for cancer cell stemness, could be a novel useful diagnostic approach for stratification of HNSCC patients based on their tumor radio resistance. CIP2A could also serve as a target protein for therapeutic radiosensitation.