Non‑small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite sig Show more
Non‑small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia‑inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient‑deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor‑associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC. Show less
The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms.
However, the mechanism(s) that transduce oxygen concentration or availability into appropriate
physiological r Show more
The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms.
However, the mechanism(s) that transduce oxygen concentration or availability into appropriate
physiological responses is less clear and often controversial. This review will make the case for
oxygen-dependent metabolism of hydrogen sulfide (H2 S) and polysulfides, collectively referred to as
reactive sulfur species (RSS) as a physiologically relevant O2 sensing mechanism. This hypothesis
is based on observations that H2 S and RSS metabolism is inversely correlated with O2 tension,
exogenous H2 S elicits physiological responses identical to those produced by hypoxia, factors that
affect H2 S production or catabolism also affect tissue responses to hypoxia, and that RSS efficiently
regulate downstream effectors of the hypoxic response in a manner consistent with a decrease in O2 .
H2 S-mediated O2 sensing is then compared to the more generally accepted reactive oxygen species
(ROS) mediated O2 sensing mechanism and a number of reasons are offered to resolve some of the
confusion between the two.
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