From molecular profiling to clinical stratification
Cervical cancer exhibits clinical heterogeneity, albeit HPV is recognised as the major etiological cause of carcinogenesis. Preventive vaccination is expected to impact incidence rates in more than 20 years from now, so in the meantime, there is an imminent need to improve treatment of cervical cancer where no prognostic and predictive biomarkers . To address this and provide safer and more efficient therapy to cervical cancer patients, the EU-funded RAIDS project proposed to define a set of stratification criteria based on molecular profiling. The idea was to identify genetic mutations and active pathways in cervical cancer that could serve as biomarkers or therapeutic targets. Cervical cancer is a model system - easy to biopsy - allowing giving molecular information on squamous cell cancers. RAIDS network collected a prospective dataset of consecutive tumour tissues, whole blood and sera from over 400 cervical cancer patients. They performed whole exome sequencing and reverse phase protein array prior to standard therapy. This data allowed the stratification of patients in different subgroups according to their molecular profile, while an association was made with clinical outcome. In addition, it helped generate a panel of approximately 600 genes that might be of clinical importance for cervical cancer. This development offers a comprehensive analysis of the pathophysiological mechanism underlying cervical cancer. Furthermore, researchers defined new biomarkers from the tumour microenvironment as a means of defining the efficacy of standard therapy. In another part of the project, the consortium performed pharmacological profiling of cell lines, which led to the identification of a group of drugs that acts in synergy with the standard treatment of advanced cervical cancers. Two novel anti-cancer therapeutic vaccines based on the HPV E7 and E8 oncoproteins were produced and clinically tested during RAIDS. Overall, the findings of the project provide important insight into dominant genomic and protein signalling pathways that are altered in cervical cancer, thereby enabling the identification of prognostic and predictive biomarkers. Dissemination of project results and of innovative practices with the help of other international organisations is expected to raise awareness for cervical cancer screening and prevention.
Keywords
Stratification, cervical cancer, HPV, RAIDS, vaccine
