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Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition

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Ways into Understanding HIF Inhibition.

Tina Schönberger¹, Joachim Fandrey¹, Katrin Prost-Fingerle¹

¹Institute of Physiology, University of Duisburg-Essen, 45147 Essen, Germany.

|January 20, 2021

Summary

Inhibiting hypoxia-inducible factors (HIFs) is crucial for cancer treatment. Understanding how HIF inhibitors work is key to developing effective anticancer drugs and ensuring patient safety.

Keywords:

FRET HIF PHD cancer hypoxia hypoxia-inducible factor inhibitor pVHL visualization

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Area of Science:

Oncology
Molecular Biology
Drug Discovery

Background:

Hypoxia, or low oxygen, is a hallmark of tumor microenvironments.
Cancer cells activate hypoxia-inducible factors (HIFs) to survive and proliferate under hypoxic conditions.
HIF pathway dysregulation is implicated in numerous solid and liquid cancers.

Purpose of the Study:

To review current classes of HIF pathway inhibitors.
To explore in vitro and in vivo techniques for understanding inhibitor mechanisms.
To highlight the importance of elucidating inhibitor modes of action for clinical application.

Main Methods:

Review of existing literature on HIF inhibitors.
Discussion of various in vitro and in vivo methodologies.
Exploration of advanced imaging techniques (luminescent, fluorescent, nanobodies) and chromatin immunoprecipitation.

Main Results:

Several drug candidates targeting HIF pathway interactions and transcription are in development, with some in clinical trials.
Open questions persist regarding the precise mechanisms of action for many HIF inhibitors.
Novel imaging and molecular techniques offer potential to clarify these mechanisms.

Conclusions:

Understanding the specific mechanisms of HIF inhibitors is essential for their successful clinical translation.
Elucidating inhibitor action is critical for optimizing efficacy and ensuring the safety of novel anticancer therapies.
Further research employing advanced techniques will accelerate the development of targeted HIF-inhibiting cancer treatments.