Abstract 1208P
Background
Identifying functionally active tumor driving signaling pathways (SP) for precision medicine is a challenge. OncoSignal pathway tests quantitatively measure activity of SP (e.g. estrogen (ER) and androgen (AR) receptor, PI3K, MAPK, Hedgehog (HH), TGF-β, Notch) on fresh frozen and formalin-fixed paraffin-embedded (FFPE) tissue samples. OncoSignal pathway analysis aimed at assessing clinically actionable SP and retrospectively predicting targeted drug response on a series of patient (pts) samples from the MOSCATO trial.
Methods
For use on FFPE material SP tests were adapted from Affymetrix microarray to an RT-qPCR 96 well testing plate (ER, AR, PI3K, MAPK, HH, Notch, TGF-β measured simultaneously), results compared per SP using Pearson correlation (pc). Affymetrix and RT-qPCR-based OncoSignal pathway analysis was performed blinded by Molecular Pathway Dx (Philips, Eindhoven) on metastatic tumor tissue samples from breast (BC), prostate cancer (PC), ovarian (OC), colon, gastric, and pancreatic cancer pts. Sample SP activity was considered tumor driving if higher than 95th percentile of SP activity in healthy tissue. Results were combined with clinical characteristics and DNA mutations found in the MOSCATO trial.
Results
Standard NGS allowed identification of actionable mutations in 4/5 BC; 13/31 PC; 6/17 OC samples. Correlation between RT-qPCR and Affymetrix pathway activity scores lies between 0.93 and 0.96 (pc). OncoSignal pathway analysis allowed identification of ER, AR, MAPK-AP1, HH, PI3K pathways alterations in BC (n=5), AR in PC (n=30); AP1, Notch, TGFβ in OC (n=17). Overall, clinically actionable tumor driving pathways were identified in all BC; 30/31 PC, 16/17 OC pts. Ongoing analysis on colon, gastric, and pancreatic cancer will be reported at ESMO.
Conclusions
OncoSignal RT-qPCR SP analysis can be performed on fresh frozen and FFPE tissue, with standard PCR equipment, fitting pathology lab workflow. SP analysis strongly improved detection of actionable targets in a subset of patients from the MOSCATO trial. OncoSignal is being prospectively validated in precision medicine studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
These results have been obtained as part of the PACMAN study that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union receives support from the European Union´s Horizon 2020 Research and innovation programme.
Disclosure
A. Van De Stolpe: Full/Part-time employment: Philips. S. Neerken: Full/Part-time employment: Philips. E. den Biezen-Timmermans: Full/Part-time employment: Philips. M. Akse: Full/Part-time employment: Philips. S. Vermeer-van de Laar: Full/Part-time employment: Philips. D. van Strijp: Full/Part-time employment: Philips. P. Martin-Romano: Leadership role, Research grant/Funding (self), Research grant/Funding (institution), Details not included: Principal/sub-Investigator of Clinical Trials and grants from many pharmaceutical companies. A. Italiano: Advisory/Consultancy, Research grant/Funding (institution), For details please ask Prof Italiano: AstraZeneca, Bayer, Epizyme, MSD, Oncosignal Philips, F. Hoffmann-La Roche, Springworks. All other authors have declared no conflicts of interest.