Optimization of a diagnostic hypoxia test for detection of aggressive cervical cancer

Siden siste rapport, dvs de siste månedene av prosjektet,har det vært arbeidet med å utvikle den nye oppfinnelsen som er generert i prosjektet og som beskriver en hypoksitest basert på genenes metyleringsnivå. Arbeidet har inkludert å evaluere styrken av en metyleringstest sammenliknet med den opprinnelige testen basert på genuttrykk.

In this project we will optimize a hypoxia test for cervical cancer that can be used as early indicator of a patient's individual risk for failure after chemoradiotherapy. Hypoxia is the most common cause of failure, and patients with hypoxic tumor need a more comprehensive treatment than is offered today. There is no such test on the market and a third of all patients die from the disease in Norway while the number is approaching 50% worldwide. By analysis of tumor biopsies from cervical cancer patients we have identified a signature of 31 hypoxia-inducible genes that associates with poor clinical outcome. In the current project we will address two major challenges that must be solved to transfer the signature into a test that is ready for proof of conc ept studies. First, we will investigate whether the number of signature genes can be reduced without loss of predictive power, since this will reduce the complexity of the test. Second, we will construct a clinical feasible test assay by evaluating PCR te chnology for detection of mRNA levels in tumor biopsies and ELISA technology for detection of protein levels in systemic blood. The possibility to use a blood sample will significantly facilitate the sampling for the test. The hypoxia test is particular ly appealing because the biology underlying tumor aggressiveness is known. The test may therefore have direct therapeutic implications in near future, since hypoxia targeting drugs already are in use for several cancer types. The test will enable medical doctors to offer hypoxia-targeted drugs combined with the conventional chemoradiotherapy for selected patients to reduce the risk of failure. Implementation of the test would therefore be a step towards a more personalized treatment of the patients, and a mean to significantly improve their prognosis and long-term well being. More than 250 women are diagnosed with invasive cervical cancer in Norway per year and may benefit from this strategy.