Targeted Therapeutic Strategies for Hypoxic TME
range of solutions and services or strategies for investigating therapeutic strategies that for target hypoxic tumor microenvironment (TME), helping researchers successfully achieve their research goals.
It is well known that hypoxia in the tumor microenvironment (TME) is an intrinsic characteristic of all solid malignancies, mainly manifested by oxygen stress, glycolysis, extracellular acidosis, accumulation of lactate, adenosine, etc., and a dynamic gradient of essential nutrient depletion. Hypoxic TME has a very significant impact on cellular metabolism, intercellular communication, epigenomics and epigenomics of tumors. Hypoxic TME is widely recognized as an independent prognostic indicator that consistently correlates with poor survival in a variety of cancer types, including breast, non-small cell lung, cervical, and ovarian cancers. Hypoxia can also lead to tumor resistance to immunotherapy through a variety of mechanisms, including innate and adaptive immunity. Therefore, hypoxia can be used as a valid biomarker to predict the outcome of immunotherapy. Because of the central role of hypoxic TME in tumor progression and treatment resistance, targeting hypoxic TME holds considerable promise in innovative immunotherapy guidance.
Fig. 1 Graphical summary that explains the effects of hypoxia on key immune cellular populations in the TME. (Wang B, et al., 2021)
Given that hypoxia in TME is a driver of tumor progression and plays a key role in remodeling the tumor stroma and promoting the emergence of immune privileges, the prospects for combined hypoxia and immunotherapy appear encouraging. Alfa Oncology has established an innovative tumor microenvironment center technology platform and is developing several technologies designed to help global collaborators develop immunotherapeutic strategies that target tumor microenvironment (TME) hypoxia, with the hope of informing clinical applications and providing some suggestions on how to target hypoxic TME synergistically with cancer immunotherapy.
It is attractive to consider controlling hypoxia in future innovative immunotherapies and several strategies targeting hypoxia have been shown to have synergistic effects with immunotherapy. The main challenge going forward is to determine which of these strategies can improve hypoxia-induced immunosuppression without compromising antitumor immunity. Additional preclinical and clinical studies are needed to explore the optimal combination of strategies and the most appropriate sequence and timing of these combinations to provide insights into tailored immunotherapies for cancer patients. Alfa Oncology has conducted specific studies based on the multiple strategies that have been proposed to overcome hypoxia in cancer, including but not limited to the following:
- Hypoxia-activated prodrugs (HAPs)
- Inhibition of the HIF signaling pathway
- Targeting important downstream hypoxia pathways (e.g., UPR (unfolded protein response) and mTOR pathways)
- Metabolic regulation
- Supplemental oxygenation
Note: The key strategies we focus on are always up to date, please contact us by email for more up-to-date and relevant information.
Alfa Oncology is committed to supporting scientists in making breakthrough scientific discoveries and developing new applications to accelerate new drug discovery and scientific diagnosis and treatment. Our high-performance scientific instruments and high-value solutions enable scientists to explore the mysteries of life at the tumor microenvironment level. Please tell us your project requirements, and we will provide you with a full service from solution to report. If you have any questions, please feel free to contact us.
- Wang B, Zhao Q, Y Zhang, et al. Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy[J]. Journal of Experimental & Clinical Cancer Research, 2021, 40(1).