Abstract 1746: Rational molecular assessment and innovative drug selection (RAIDs): Paving the way to personalized medicine in cervical cancer

Abstract

Cervical cancer (CC) is the fourth most common cause of cancer deaths in women worldwide, for which prognostic and predictive biomarkers are largely lacking. RAIDs is a EU-funded project on cervical cancer that spans seven European countries. The main objective of the RAIDs project is to use this tumor type, which is easily accessible for repeated biopsies, to learn how to stratify patients into targeted therapies. The project includes: 1) a cognitive cohort study (BioRAIDs), one of the first prospective trials intended to define patient stratification for targeted therapies, 2) a targeted clinical trial using an HPV directed vaccine and 3) preclinical studies aiming at assessing new treatment strategies. Molecular analysis on quality controlled tumor and sera samples from 400 patients include Next Generation Sequencing at SeqOmics (Hungary), PIK3CA mutations detection in circulating tumor DNA at Erasmus MC (Netherlands), Reverse Phase Protein array and HPV insertion sites analyses at Institut Curie (France) and immune-microenvironment analyses at CGOA (Netherlands). In addition, 20 CC cell lines have been profiled pharmacologically using a panel of drugs which potentially synergize with “standard treatment”. The present poster will mainly focus on the Reverse Phase Protein Array (RPPA) results of BioRAIDs and how these relate to the genomic profiling and to patient outcome. More than 150 cryopreserved baseline (before treatment) samples and 23 CC cell lines have been screened by RPPA. From these, whole exome sequencing is available for 92 patient samples. Stratification of patients based on proteomics and genomics has evidenced different subgroups (clusters) of patients displaying specific molecular characteristics. Genomics data and proteomics data both demonstrate that these clusters differ notably in the pathways of oxidative phosphorylation, glycolysis and DNA repair. Patient response to treatment is assessed by the presence or absence of residual tumor at six months after treatment. The correlation of proteomics and genomics data with these clinical data is ongoing and will identify putative predictive biomarkers. Correlation of protein data with response to drugs treatment in 20 CC cell lines has identified several potential biomarkers, some of which again relate to (glucose) metabolism. In conclusion, we here present new evidence for molecular subgroups of cervical cancer that could benefit from different treatment options. Notably, our data suggest that the metabolism/glycolysis pathways are a major effector in CC and constitute a potential therapeutic target in a subset of patients. This project has received funding from the European Union’s Seventh Program for research, technological development and demonstration under grant agreement No 304810. Citation Format: Leanne de Koning, Bérengère Ouine, Aurélie Cartier, Els M. Berns, Kirsten Ruigrok-Ritstier, Corine Beaufort, Balazs Balint, Attila Kereszt, Gemma Kenter, Sanne Samuels, Ekaterina S. Jordanova, Emmanuelle Jeannot, Heiko von der Leyen, Marina Popovic, Windy Luscap-Rondof, Vonick Sibut, Choumouss Kamoun, Isabel Britto, Claudia Rincon, Philippe Hupé, Maud Kamal, Suzy M. Scholl. Rational molecular assessment and innovative drug selection (RAIDs): Paving the way to personalized medicine in cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1746. doi:10.1158/1538-7445.AM2017-1746