Rational application of targeted therapeutics in mucinous colon/appendix cancers with positive predictive factors.

ABSTRACT: Molecular-targeted therapies have demonstrated disappointing results against most advanced solid cancers. This may largey be attributed to irrational drug use against unselected cancers. We investigated the efficacy of dual MEK-PI3K drug therapy against KRAS mutated mucin 2 (MUC2)-secreting LS174T cells and patient-derived ex vivo and in vivo models of KRAS mutated mucinous colon/appendix cancers. These tumors demonstrate unique phenotypic and genotypic features that likely predict sensitivity to this targeted co-therapy. Co-treatment with MEK inhibitor (trametinib) and PI3K inhibitor (pictilisib)-induced synergistic cytotoxicity and intrinsic mitochondrial-mediated apoptosis in LS174T cells and tumor explants in vitro. Dual drug therapy also induced endoplasmic reticulum stress (ERS)-asso

SUBMITTER: Dilly A 

PROVIDER: S-EPMC7050077 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature