The Response of HMGB1 to Small Molecule Inhibitors and Natural Products using In-Vitro and In-Vivo Lung Cancer Models

In the United States, lung cancer continues to claim thousands of lives each year, with little improvement in survival over the past decade. Lung cancer in these settings is diagnosed at later stages, where the current therapeutic options have proven less effective. The advent of immune checkpoint inhibitors has improved the survival of some lung cancer patients; however, those diagnosed later still have a low overall survival even with treatment. Therefore, innovative approaches in diagnosis and treatment could have a broadly positive impact on patient outcomes. Our study aimed to investigate whether treatment with deacetylase or HMGB1 inhibitors change the levels of secreted HMGB1 or increase survival in cancer patients to untreated control. Using Rayyan, blinded analysis of 490 items were dissected out and studied with the purpose of inclusion or exclusion to specific criteria. The data included pertained to current research on the response of HMGB1 to available cancer therapies using in-vitro and in-vivo models. We concluded, studies that worked with HMGB1 inhibitors conveyed an increase in HMGB1 levels inside the cell, therefore leading to a decrease in HMGB1 release. Studies with HDAC inhibitors indicated a decrease in HMGB1 levels inside the cell and an increased HMGB1 release, with the exception of sodium butyrate. Sodium butyrate levels of HMGB1 decreased inside and outside the cell, concluding that the effect of HMGB1 may be in the gene expression. Going forward we will enroll patients into studies to measure the levels of HMGB1in tumors and blood.