Cholangiocarcinoma

Interim analysis of the part 2 dose-expansion portion of an ongoing 2-part phase 1 Japanese study shows that the FGFR1 tyrosine kinase inhibitor E7090 was active with a manageable safety profile in CCA patients with FGFR2 gene fusion.

AKT and NOTCH intracellular domain (NICD) targets YAP and SOX9 might be potential targets for therapeutic intervention in intrahepatic CCA subsets, while cholestatic injury or NASH might induce hepatocyte-to-cholangiocyte reprogramming that increases risk of intrahepatic CCA.

Preliminary results of a phase 2 study suggest that the addition of the PI3K inhibitor copanlisib to chemotherapy in the first-line setting was not associated with survival benefit in patients with advanced CCA.

Preclinical data implicate the ELR+ chemokine/CXCR2 axes in the pathogenesis of CCA, warranting further studies to define its role in CCA.

Data reported at the ASCO 2020 GI Cancers Symposium indicate that treatment with neoadjuvant definitive chemoradiation followed by orthotopic liver transplantation was associated with better outcomes compared with definitive chemoradiation alone in patients with unresectable extrahepatic/hilar CCA.

Preclinical evidence using an genetically engineered mouse model of IDH1-mutated intrahepatic CCA indicates that the selective IDH1 inhibitor ivosidenib mediates its antitumor activity by promoting hepatic progenitor-cell differentiation, and inducing T-cell–mediated antitumor immune response.

Preclinical evidence presented at the AACR meeting implicates PKN2 signaling in resistance mechanisms in patients with FGFR2 fusion–positive intrahepatic CCA.

Patient-derived tumor organoids may have clinical application to predict drug responses in a personalized treatment setting; they have shown concordance with actionable genomic anchors and retrospective treatment outcomes.

Emerging data suggest that patient-derived 3-dimensional organoid model of intrahepatic CCA may allow personalized drug screening for active single agents or drug combinations similar to patient-derived xenograft models.