KRASG12D inhibition in pancreatic cancer: Fas expression facilitates immune clearance

In an article in this issue of Developmental Cell and in a second paper in Cancer Cell, Mahadevan et al. demonstrate that KrasG12D suppression remodels the immunosuppressive microenvironment of KrasG12D pancreatic cancers, recruits activated CD8+ cytotoxic T cells, and epigenetically upregulates Fas expression in cancer cells, leading to tumor clearance via Fas/FasL-mediated apoptosis. In an article in this issue of Developmental Cell and in a second paper in Cancer Cell, Mahadevan et al. demonstrate that KrasG12D suppression remodels the immunosuppressive microenvironment of KrasG12D pancreatic cancers, recruits activated CD8+ cytotoxic T cells, and epigenetically upregulates Fas expression in cancer cells, leading to tumor clearance via Fas/FasL-mediated apoptosis. Elimination of oncogenic KRAS in genetic mouse models eradicates pancreatic cancer by inducing FAS-dependent apoptosis by CD8+ T cellsMahadevan et al.Developmental CellAugust 24, 2023In BriefMahadevan et al. report that KG12D epigenetically upregulates FAS death receptors in pancreatic cancer cells, with KRASG12D depletion enabling FASL-expressing CD8+ T cells to eradicate tumors. Another study using an inhibitor against KRASG12D in multiple PDAC models, by Mahadevan et al. in Cancer Cell, shows similar mechanisms of tumor regression. Full-Text PDF KRASG12D inhibition reprograms the microenvironment of early and advanced pancreatic cancer to promote FAS-mediated killing by CD8+ T cellsMahadevan et al.Cancer CellAugust 24, 2023In BriefMahadevan et al. demonstrate that the oncogenic KRASG12D inhibitor MRTX1133 reverses early and advanced PDAC growth and remodels the tumor microenvironment. MRTX1133 induces FAS expression in cancer cells and promotes CD8+ T cell mediated death. Full-Text PDF