Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide, with metastases to the liver being responsible for very poor diagnoses. It is therefore crucial to develop a therapeutic approach to target these metastases. Phosphoinositide-3-kinase (PI3-K) is upregulated in many cancers, including CRC; and its cascades include various downstream lipid effectors. MALDI-MS imaging has been used to investigate the effect of a PI3-K inhibitor GDC-0941 on lipid profiles in CRC liver metastases.

An in-house mouse model was used to generate CRC tumours. Mice that underwent drug therapy were administered two doses of 50m/kg of GDC-0941. Vehicle and drug treated tumours were flash-frozen and sectioned for MALDI imaging .Adjacent sections were kept for immuno fluorescence. MALDI imaging and MS/MS experiments were carried out on the MALDI-7090 (Shimadzu, UK).

Clear lipid profile changes occur between non-treated and treated tumours, with certain phoshphatidylcholines showing a decrease in abundance after drug addition. Comparing MALDI images to H&E stains reveal which lipids are localised to necrotic, tumour, normal tissue; or those which are found heterogeneously in the tumour, and are hence significant for effective therapy. MALDI images have also been compared to immunofluorescence to show which lipids co-localise with immune cell infiltration. Future work will involve elucidating exactly what lipid mechanisms are occurring in these tumours to give the lipid changes seen as a result of PI3-K inhibition.