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Systemic Hypoxia and Tumor Growth: A new research has revealed that systemic hypoxia can help in suppressing tumor growth. Systematic hypoxia is a condition when oxygen is reduced in the body in a controlled manner. This can stop the tumor from growing. Ayush Midha, a research scholar at the University of California San Francisco, has conducted this study with the help of many institutes and researchers. Ayush has shared the pre-prints related to this research on X.
Can systemic hypoxia prevent tumor growth? Researchers started investigating this question on the basis of two different observations. The first observation was that tumor-localized hypoxia is associated with poor prognosis. Secondly, people who live at high altitude, the air is thinner there. Cancer mortality rate is low in such people.
Little is known about how systemic hypoxia affects tumor progression, so researchers exposed mice with solid tumors to different oxygen levels: 21% (normoxia), 11% (moderate hypoxia) and 8% O2 (hypoxia). It was observed in the study that tumors grew very little in hypoxic rats.
How will hypoxia affect different cancer cell lines? To find out this, researchers used a platform named GENEVA created by Johnny Yu and Hani Gudarjee. In this, 20 pooled cancer cell lines were implanted in normoxic and hypoxic mice and single-cell RNA-sequencing was done after 8 days.
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Using the GENEVA data, the researchers found that some cell lines survived hypoxia better than others and that those cell lines activated genes involved in the synthesis of new purine nucleotides.
Using transcriptomics data, the researchers observed that hypoxic mice had lower levels of purine nucleotides in smaller tumors, which may reduce cancer cell growth.
Nucleotides can come from two sources: de novo synthesis, which requires a lot of energy. The second is salvage, which requires a lot of nucleobase substrate. The study measured the contribution of each pathway; Hypoxic tumors suppressed de novo synthesis, causing purine pools to become smaller.
Researchers think hypoxia slows tumor growth, but could it be used with existing cancer therapies? The answer is that hypoxia can enhance the tumor suppressive effects of the chemotherapy drug gemcitabine and anti-CTLA4 immunotherapy.
However, treating real patients with hypoxia will pose practical difficulties. Recently, researchers showed that hypoxistat, a small molecule that increases hemoglobin’s binding affinity for oxygen, could mimic the effects of hypoxia and the drug even slowed tumor growth! (All Images Credit –
