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SCI 15 October 2024 Combined KRAS inhibition and immune therapy generates durable complete responses in an autochthonous PDAC model (Cancer Discov, IF: 29.7) Liu Y, Han J, Hsu W-H, et al: Combined KRAS inhibition and immune therapy generates durable complete responses in an autochthonous PDAC model. Cancer Discov 10.1158/2159-8290.CD-24–0489, 2024 Abstract Pancreatic ductal adenocarcinoma (PDAC) resists conventional chemo/radiation and immunotherapy. In PDAC, oncogenic KRAS (KRAS*) drives glycolysis in cancer cells to consume available glucose and produce abundant lactate, creating profound immune suppression in the tumor microenvironment. Here, we combined KRAS* inhibition with agents targeting the major arms of the immunity cycle: CXCR1/2 inhibitor for myeloid cells, antagonistic anti-LAG3 antibody for T cells, and agonistic anti-41BB antibody for dendritic cells. This combination elicited robust anti-tumor regression in iKPC mice bearing large autochthonous tumors. While untre
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