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: Livio Mallucci, Valerie Wells
• Journal: Drug discovery today (Drug Discov Today) Vol. 19 Issue 4 Pg. 383-7 (Apr 2014) ISSN: 1878-5832 [Electronic] England
• PMID: 24291216 (Publication Type: Journal Article, Review)
• Copyright: Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Galectins
• KRAS protein, human
• Proto-Oncogene Proteins
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Animals
• Galectins (metabolism)
• Humans
• Neoplasms (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins p21(ras)
• ras Proteins (genetics, metabolism)