Chemoradiotherapy is the standard of care for cervix cancer, and reduces the risk of recurrence and disease-related death However, the response is highly heterogeneous, and there is a pressing need for more accurate predictors of radio-curability, to improve prognosis and prediction of response to radiotherapy. Tumour hypoxia is associated with cancer aggressiveness, and hypoxia-targeted or activated drugs are in development for multiple cancers. Biomarkers of hypoxia that predict treatment response would be of particular value.
Scientists at Institute of Cancer Research, Oslo University Hospital, have developed the following gene expression signatures differentiating cervical cancers based on their aggressiveness:
Hypoxia signature (31 genes; defined a 6-gene optimal classifier) Chromosome instability signature 1 (12 genes; defined a 4-gene optimal classifier) Chromosome instability signature 2 (8 genes; definition of optimal classifier ongoing)
The signatures have been validated in independent clinical cohorts and successfully transferred to qPCR-based analysis platforms. The hypoxia and chromosome instability signatures are thought to capture different aggressiveness factors, and may therefore be combined in the same eventual prognostic test. The hypoxia signature may also potentially be a companion diagnostic test, useful for patient selection and prediction of response to therapy for hypoxia-activated drugs in clinical development.
We plan to implement the tests in future prospective trials at Oslo University Hospital, preferably together with industrial partners.
The signatures are protected by the following patent applications:
Hypoxia signature: WO 2013/124738 A2 (pending in multiple major jurisdictions) Chromosome instability signature 1: US 2011/0224088 A1 (pending in US) Chromosome instability signature 2: WO 2014/072832 A2 (pending in multiple major jurisdictions)