Combined Targeting of AKT and mTOR Synergistically Inhibits Formation of Primary Colorectal Carcinoma Tumouroids <i>In Vitro</i>: A 3D Tumour Model for Pre-therapeutic Drug Screening

Background: Pre-therapeutic analysis of three-dimensional spheroid cultures primary tumour samples is a promising approach assessing susceptibility to potential treatment. The phosphatidylinositol-3-kinase/AKT serine/threonine kinase/mammalian target rapamycin (PI3K/AKT/mTOR) signalling pathway frequently activated in colorectal cancer (CRC). In previous work, we showed combined inhibition AKT and mTOR be highly synergistic cell lines from patients with hepatocellular carcinoma cholangiocarcinoma vitro as well vivo murine xenograft models. Materials Methods: Patient-derived HROC80 T1 M1, HROC147 T0 HROC147Met, HROC277 M1 HROC277Met2 were treated inhibitor MK2206, RAD001 or the combination both drugs. sensitivity these was evaluated by calculation combinatory indices after bromodeoxyuridine assays respective pathways western blotting. Furthermore, dual confirmed mouse model. Additionally, CRC four embedded matrix analyzed measurement area. Results: this study, demonstrate that treatment MK2206 resulted strong effects on growth several reduced patient-derived xenotransplantation model vivo. Interestingly, response varied between derived lesion liver metastasis same patient. addition, inhibitors tumouroid all patient samples, vitro. Conclusion: Our data exhibits proliferation cells may for CRC.