Since we discovered the novel PCNA interacting motif APIM in 2009, the primary objective in this project has been to explore how the APIM-PCNA interactions are regulated, and which processes are affected by blocking these interactions. The secondary objective has been to develop a peptide drug targeting PCNA for use in cancer therapy. Outcomes: From 2012-2022 we have published 15 papers covering different aspects of this project. We have shown that the affinity of APIM for PCNA is increased during cellular stress, that the interaction is necessary for proper function of several DNA repair and DNA damage tolerance proteins, as well as the metabolic enzyme ENO1. We have developed an APIM-containing cell penetrating peptide, ATX-101, that block multiple APIM-PCNA interactions and thereby sensitises cancer cells for multiple different treatments. This drug was recently evaluated in a clinical Phase I study by the NTNU spinoff company APIM Therapeutics founded by professor Otterlei and found to be well tolerated and to have cancer stabilizing activity in advanced cancer patients. Data obtained from the research group at IKOM has shown that the PCNA has non-canonical roles as a scaffold protein in cytosol, directly regulation primary metabolism, cellular signaling and apoptosis, which likely is important for the cancer stabilizing effects observed in the clinical Phase I study.