The PI3K/Akt pathway’s importance in cancer is partly attributable to PI3K’s (phosphatidylinositol 3-kinase’s) association with oncogenic growth factor receptors, notably for epidermal growth factor, platelet-derived growth factor, and mesenchymal transition factor. The pathway is also prone to mutations associated with oncogenesis, including changes in the catalytic subunit of PI3K that occur in prostate, breast, endometrium, urinary tract, and colon cancers.
Similarly, mutations of the lipid phosphatase PTEN that normally serves to deactivate the PI3K/Akt pathway are found in cancers of the endometrium, brain, skin, and prostate, while mutations in the protein kinase Akt, which is downstream of PI3K, are overexpressed in head and neck squamous cell carcinoma, and in pancreatic and ovarian cancers. Eight drugs targeting the PI3K/Akt pathway are in clinical trials.
Immunotherapies are under development against molecules on CSC surfaces that differ in quantity and/or quality from those on normal cells. ImmunoCellular Therapeutics’ ICT-121 vaccine elicits an immune response using a nine amino-acid epitope of the cell marker CD133.
The company is also developing mAbs that identify CSCs for destruction by the immune system. ICT-69, which was recently outlicensed to Roche, uses an antigen specific to ovarian cancer and multiple myeloma, while another project focuses on two cell adhesion molecules, CEACAM5 and -6, that are expressed by precancerous colon and breast cells.
MabCure has a similar program, but one that targets less-antigenic cell markers, based on an assumption that they have escaped immune detection. The company has prepared antibodies against ovarian, colorectal, and prostate cancers, as well as melanoma, for diagnostic tests, and later for therapeutic agents.