Abstract 1252P
Background
Although genomic profiling is commonly used to characterize tumors, clinical treatment successes are limited. For many tumors no actionable results are found. Furthermore it is often unknown if an identified genomic alteration affects cell functionality. By using the OncoSIGNal platform technology the actual tumor-driving signal transduction pathway (STP) activities can be quantified resulting in unique tumor profiling. Using healthy tissue as reference, high pathway activities can be determined in an individual patient giving guidance for personalized treatment. Recently we demonstrated for breast and ovarian tumors this approach leading to highly personalized actionable results, which can be used in the FINPROVE study. We further expanded the approach to other tumors. Here the results of STP profiling of skin tumors are presented.
Methods
Using the mRNA-based OncoSIGNal pathway activity profiling PCR test (InnoSIGN), STP activities of 7 pathways (AR, ER, PI3K, MAPK, HH, TGFβ and Notch) in 25 samples from healthy skin tissue, 35 primary melanoma, 39 metastatic melanoma and 18 basal cell carcinoma (BCC) were quantified and expressed on a scale from 0-100. Only samples with ≥ 50% epithelial cell content were included. High pathway activity in a tumor sample was concluded when its score was higher than the 95th percentile of reference skin STP activity.
Results
Different profiles of high pathway activity were found across skin tumor types: Table: 1252P
HH | MAPK | PI3K | TGFβ | |
BCC (n=18) | 94% | 44% | 22% | 11% |
Primary melanoma (n=35) | 14% | 6% | 51% | 6% |
Metastatic melanoma (n=39) | 18% | 15% | 38% | 5% |
Further, within the skin tumor types, patient specific STP profiles were observed.
Conclusions
Using the OncoSIGNal test, actionable STP profiles were determined in samples from melanoma and BCC patients, creating opportunity for personalized targeted treatment. The OncoSIGNal test will be employed in the FINPROVE trial to identify patient specific actionable targets in several tumor types using tissue specific references.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
InnoSIGN.
Funding
Has not received any funding.
Disclosure
D. Keizer, E. den Biezen, A. Van Brussel: Financial Interests, Institutional, Full or part-time Employment: InnoSIGN. E. Niemela, S. Karjalainen: Financial Interests, Institutional, Full or part-time Employment: Helsinki University Hospital. Y. Wesseling Rozendaal: Financial Interests, Personal and Institutional, Full or part-time Employment, Full Time Employee: InnoSIGN. M.V.J. Mustonen: Financial Interests, Institutional, Full or part-time Employment: FICAN South, Helsinki University Hospital. K. Peltola: Financial Interests, Institutional, Full or part-time Employment: Comprehensive Cancer Center.
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