title: The end of KRAS, and other, cancers? A new way forward.
abstract: Mutant KRAS, as well as other mutant driver genes and epidriver genes, is a dominant determinant of resistance to cancer therapeutics. The recent introduction of targeting therapies based on drugs that inhibit the kinase catalytic function of nodal points along the Ras/extracellular-signal-regulated kinase (ERK) and the phosphatidylinositol-3-kinase (PI3K)/Akt cascades is meeting with limited success. Against this background, recent evidence shows that the β-galactoside-binding protein (βGBP) molecule, a physiological PI3K inhibitor, is a potent inducer of apoptosis in KRAS-mutant cancer cells (along with other aggressive cancer cells of different genetic makeup) and that it is therapeutically effective in vivo. Absence of p53 or phosphatase and tensin homolog (PTEN) tumor suppressor function or added activating PI3K mutations does not affect βGBP function. In contrast to the concept of one drug against one target, βGBP operates through alternative physiological routes.
authors.affiliation: School of Biomedical and Health Sciences, King's College London, London, UK. Electronic address: livio.mallucci@kcl.ac.uk.
authors.forename: Livio
authors.initials: L
authors.lastname: Mallucci
authors.affiliation: NYU in London, London, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Wells
mesh_terms: D000818:Animals; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D037161:Galectins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins