Livio Mallucci and Valerie Wells
King├ó┬?┬?s College London, UK
NYU in London, UK
Posters & Accepted Abstracts: Med chem
Current anticancer therapies have two fundamental bases. One is chemical; the killing of cancer cells by the use of small molecular inhibitors that block crucial functional nodes downstream of Ras or downstream of PI3K. The other is immunological; the use of antibodies which block immune checkpoints or the modulation of cytokines involved in cancer immune interactions. Against this therapeutic background, stands the discovery that monomeric beta-galactoside binding protein (├?┬▓GBP) a molecule recently identified as a cytokine produced by activated CD4+ and CD8+ T cells and by CD8+ memory cells is a specific physiological inhibitor of PI3K and Ras activity, valid intervention points for cancer therapy. Furthermore, ├?┬▓GBP is also a modulator of cytokines involved in oncogenicity, valid intervention targets for cancer immunotherapy. By controlling the PI3K and Ras cascades ├?┬▓GBP activates apoptotic pathways in cancer cells, but not in normal cells, independently of activating oncogenic mutations, absence of tumor suppressor function and drug resistance phenotype. As a therapeutic, ├?┬▓GBP is a strong suppressor of xenograft growth of human tumors carrying Kras mutations and TP53 deficiency in animal models. By inhibiting growth and survival signaling and by raising the expression of cytokines that promote antitumor immunity and abrogating at the same time the expression of cytokines that promote tumor functions ├?┬▓GBP exerts a dual anticancer action not paralleled by other anticancer agents.
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