Current success rate of anti-cancer therapies remain unsatisfactory, with almost inevitable development of resistance to conventional drugs in most cancers including colorectal cancer (CRC) and chronic myeloid leukemia (CML). Predictive biomarkers are needed to increase the chance of therapeutic success.
Fas (CD95, APO-1 or TNFRSF6) is a key protein that can promote apoptosis and cancer cell survival depending on the disease context. It influences the outcome of many chemotherapies and targeted therapies. Until now, there is no means to predict Fas signaling mode, which is essential to Fas-targeted therapies.
The researchers have discovered that death domain tyrosine phosphorylation of Fas is correlated with CRC stages, cancer cells survival, resistance of CRC and CML cells to currently used drugs, relapse, and therapeutic response.
Differential tyrosine phosphorylation of Fas:
- can be used as a unique biomarker for patient stratification and treatment monitoring (theranostic tool), guiding the choice between activation and inhibition of Fas signaling, predicting and early-detecting resistance outset to anticancer therapies such as imatinib and cisplatin,
- is detectable using two new and monoclonal antibodies (working at least in immuno-histochemistry, ELISA and immunoblotting) specifically detecting phosphorylation levels of tyrosine 232 and 291 of Fas in a biological samples of patients (blood sample, biopsy…).
Ongoing proof of concept on additional human samples to confirm the diagnostic and predictivity values of the tool
Assessment on different cancers (CRC, CML …)