FASTBASE SOLUTIONS is an imaging system, composed of a proprietary adapted microscope powered by software based on a proprietary time-resolved A-FRET technique. It determines both molecular and cell-cell interactions, enabling the evaluation of clinical efficiency of personalised cancer treatments.
FASTBASE SOLUTIONS is able to detect biomarkers that define the best treatment with an up to fourfold higher sensitivity and up to threefold higher selectivity with respect to current market technologies (immunohistochemistry and proximity ligase assays).
FASTBASE SOLUTIONS provides a fast and efficient platform technology to measure drug target function. The benefits of precision medicine that can be provided by FASTBASE SOLUTIONS would be to deliver treatment to patients selected to respond to therapy.
Quantitative prognosis of novel biomarkers for Clear Cell Renal Cell Carcinoma (ccRCC) patients
Tumour heterogeneity in (ccRCC) can often be missed by current sampling methods, therefore novel biomarkers need to be identified. An example is the activation state of an oncoprotein known as Protein Kinase B (PKB/Akt). We have used FASTBASE SOLUTIONS Technology to test whether the activation state of PKB can be utilised as a prognosis.
PKB/AKT activation state correlates with poor overall survival in ccRCC
Clear cell renal cell Carcinoma (ccRCC) tumours in paraffin-embedded fixed tissue microarrays. Upper panels are immunohistochemistry staining showing Low (left) and High (right) grade ccRCCs. The two lower panels are acquired using the FASTBASE SOLUTIONS setup. The intensity images (corresponding to protein expression levels method used classically in immunohistochemistry) of PKB/Akt and the activation of Akt (pAkt) expression levels do not yield differences. However, Lifetime maps do yield significant differences between primary and metastatic ccRCC samples (indicated by the punctate red regions (last panel right-hand side). The survival clinical graphs show that PKB/Akt activation state correlates with poor overall survival in ccRCC. The left-hand side panel shows that survival outcomes related to PKB/Akt activation as determined by FASTBASE SOLUTIONS Technology or by conventional IHC (right panel). A highly significant difference was observed between the high activation states of PKB/Akt. However, no difference was detected when survival is determined by immunohistochemistry (routine methods) intensity of the activation state of PKB/Akt. (Figure adapted from Miles et al 2017 Clinical BBA).
FASTBASE SOLUTIONS platform
The platform consists of multiple frequency fluorescence lifetime imaging microscopes (mf-FLIM), proprietary assay kits, and a user-friendly software for automated mapping and image acquisition of cancer cells and tissue.
The assay kits, to be used before inserting the sample in the mf-FLIM, consist of matched primary and secondary reagents for detection/quantification of specific antigens in cells.
The mf-FLIM is the delivery method for the software that detects the amplified signals derived from fluorescently labelled molecules immediately after excitation. These signals are crucial because they indicate protein activation states and protein interactions, which are markers of disease to be targeted by selected drugs. The technique can detect the number of interactions between two molecules, which is relevant in order to understand the spread of a tumour.
The software elaborates the automatically collected images, allowing us to understand the cell response to drugs and define the most effective treatments for each patient.