Abstract: As disclosed herein, inhibition of the ornithine decarboxylase 1-driven pathway can restore immunotherapeutic efficacy in lung cancer with lost STK11 function. Therefore, disclosed herein are compositions and methods for treating a lung cancer in a subject using an ornithine decarboxylase (ODC) inhibitor, such as difluoromethylornithine. In particular, disclosed is a method for using an ODC inhibitor to sensitize a lung cancer to immunotherapy. The method can involve assaying the subject for STK11 function. The method can also involve treating the subject with an immunotherapy, such as anti-PD-1/PD-L1 immunotherapy.

Abstract: Biomarkers, methods, assays, and kits are provided for predicting the efficacy of adjuvant chemotherapy (ACT) in a subject with early-stage non-small cell lung cancer (NSCLC).

Abstract: A small molecular inhibitor of E2F (HLM006474) was identified using a computer-based virtual screen and the known crystal structure of the DNA bound E2F4/DP2 heterodimer. Treatment of multiple cell lines resulted in the loss of intracellular E2F4 DNA-binding activity. Overnight exposure to HLM006474 resulted in down regulation of total E2F4 protein as well as several known E2F targets. The effects of treatment on different cell lines included a reduction in cell proliferation and an increase in apoptosis. Apoptosis was induced in a manner distinct from cisplatin and doxorubicin. E2F4-null MEFs (mouse embryo fibroblasts) were less sensitive than wildtype counterparts to the apoptosis-inducing activity of the compound revealing its biological specificity. A375 cells were extremely sensitive to the apoptosis-inducing activity of the compound in two-dimensional culture and HLM006474 was a potent inhibitor of melanocytes proliferation and subsequent invasion in a three-dimensional tissue culture model system.

Abstract: A small molecular inhibitor of E2F (HLM006474) was identified using a computer-based virtual screen and the known crystal structure of the DNA bound E2F4/DP2 heterodimer. Treatment of multiple cell lines resulted in the loss of intracellular E2F4 DNA-binding activity. Overnight exposure to HLM006474 resulted in down regulation of total E2F4 protein as well as several known E2F targets. The effects of treatment on different cell lines included a reduction in cell proliferation and an increase in apoptosis. Apoptosis was induced in a manner distinct from cisplatin and doxorubicin. E2F4-null MEFs were less sensitive than wildtype counterparts to the apoptosis-inducing activity of the compound revealing its biological specificity. A375 cells were extremely sensitive to the apoptosis-inducing activity of the compound in two-dimensional culture and HLM006474 was a potent inhibitor of melanocytes proliferation and subsequent invasion in a three-dimensional tissue culture model system.