Overcoming tumor hypoxia:factors influencing the efficacy of the hypoxia-activated prodrug CP-506

Hypoxia – defined as a low level of oxygen – is a common characteristic of the majority of solid tumors and contributes to disease progression and resistance to conventional therapies. Overcoming tumor hypoxia is therefore a promising strategy to improve cancer treatment. Hypoxia-activated prodrugs (HAP) are therapeutic agents that are activated only in hypoxic regions of the tumor and not in healthy tissues. This thesis investigated a novel HAP, called CP-506. CP-506 was found to have potent antitumor effects in a broad range of cancer types, both as a monotherapeutic agent, but even more so in combination with radiotherapy and immunotherapy. In addition, the degree of hypoxia and genetic status of the tumor were strong determinants of the tumoral response to CP-506. Based on findings in this thesis, CP-506 will be tested for the first time in humans in a phase 1/2a clinical trial soon