Directing Hypoxic Tumor Microenvironment and HIF to Illuminate Cancer Immunotherapy's Existing Prospects and Challenges in Drug Targets.

Abstract

Cancer is now also reflected as a disease of the tumor microenvironment, which is primarily supposed to be a decontrolled genetic and cellular expression disease. Over the past two decades, significant and rapid progress has been made in recognizing the dynamics of the tumor's microenvironment and its contribution to influencing the response to various anti-cancer therapies and drugs. Modulations in the tumor microenvironment and immune checkpoint blockade are interesting in cancer immunotherapy and drug targets. Simultaneously, the immunotherapeutic strategy can be implemented by modulating the immune regulatory pathway; however, the tumor microenvironment plays an essential role in suppressing the antitumor's immunity by its substantial heterogeneity. Hypoxia inducible factor (HIF) is a significant contributor to solid tumor heterogeneity and a key stressor in the tumor microenvironment to drive adaptations to prevent immune surveillance. Checkpoint inhibitors here halt the ability of cancer cells to stop the immune system from activating, and in turn, amplify the body's immune system to help destroy cancer cells. Common checkpoints that these inhibitors affect are the PD-1/PDL1 and CTLA-4 pathways, and important drugs involved are Ipilimumab and Nivolumab mainly, along with other drugs in this group. Targeting the hypoxic tumor microenvironment may provide a novel immunotherapy strategy, break down traditional cancer therapy resistance, and build the framework for personalized precision medicine and cancer drug targets. We hope that this knowledge can provide insight into the therapeutic potential of targeting hypoxia and help develop novel combination approaches of cancer drugs to increase the effectiveness of existing cancer therapies, including immunotherapy.