The IDO1/TDO2-AHR pathway drives immunosuppressive tumor microenvironments and high pathway activity is correlated with poor prognosis in many cancer types. AHR is a transcription factor activated by kynurenine and other ligands and is an ideal therapeutic target for reversing the broad immunosuppressive activities mediated by this pathway. McGovern and colleagues introduce IK-175, a selective small molecule that inhibits AHR in vitro and in vivo. IK-175 inhibits tumor growth alone and combined with anti-PD-1 antibodies and reverses immune suppression and increases pro-inflammatory cytokines and effector immune cells in preclinical tumor models. These data provide rationale treating cancer patients with IK-175.

Glioblastoma (GBM) remains an incurable malignancy due to treatment resistance and inevitable recurrence. The hypoxic microenvironment in GBM promotes glioma stem cells via epithelial to mesenchymal transition, which are responsible for resistance, recurrence, and invasive nature of GBM. Here, Kannappan and colleagues have shown that Disulfiram, an anti-alcoholism drug effectively inhibits...

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