Title:Directing Hypoxic Tumor Microenvironment and HIF to Illuminate Cancer
Immunotherapy's Existing Prospects and Challenges in Drug Targets
Volume: 23
Issue: 5
Author(s): Suman Kumar Ray and Sukhes Mukherjee*
Affiliation:
- Department of Biochemistry, All India Institute of Medical Sciences,
Bhopal, Madhya pradesh-462020, India
Keywords:
Tumor microenvironment, hypoxia, HIF, immunotherapy, checkpoint inhibitors, immune surveillance, precision medicine.
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.
