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    2years
    Synergistic effects of the combination of Kras (G12C) with SHP2, ERK 1/2, mTORC1/2 or XPO1 inhibition for the treatment of Kras (G12C) mutated cancer (AACR 2022)
    This study tested the antitumor effects induced by the combination of ATG-012, a KRAS G12C inhibitor, with SHP2 inhibitor (ET0038), ERK 1/2 kinase inhibitor (ATG-017), mTORC1/2 kinase inhibitor (ATG-008) or XPO1 inhibitor (selinexor), in preclinical tumor models. The in vivo combinations of the drugs were tested in NCI-H358 (non-small cell lung cancer) and Mia-Paca-2 (pancreatic cancer) CDX mouse model. Strong in vivo synergism has been observed for the combination of a Kras (G12C) inhibitor (ATG-012) with a SHP2 inhibitor, ERK 1/2 inhibitor, mTORC1/2 inhibitor or XPO1 inhibitor, suggesting promising clinical therapeutic strategies for cancer patients carrying the KRAS G12C mutation.
    IO biomarker
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    KRAS (KRAS proto-oncogene GTPase)
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    KRAS mutation • KRAS G12C • PTEN mutation • RAS wild-type • KRAS G12 • MTOR mutation
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    Xpovio (selinexor) • onatasertib (ATG-008) • ATG-012 • ETS-001 • tizaterkib (ATG-017)