Abstract
Symptoms associated with lung cancer mainly consist of cancer-associated pain, cough, fatigue, and dyspnea. However, underlying mechanisms of lung cancer symptom clusters remain unclear. There remains a paucity of effective treatment to ameliorate debilitating symptoms and improve the quality of life of lung cancer survivors. Recently, extracellular ATP and its receptors have attracted increasing attention among researchers in the field of oncology. Extracellular ATP in the tumor microenvironment is associated with tumor cell metabolism, proliferation, and metastasis by driving inflammation and neurotransmission via P2 purinergic signaling. Accordingly, ATP gated P2X receptors expressed on tumor cells, immune cells, and neurons play a vital role in modulating tumor development, invasion, progression, and related symptoms. P2 purinergic signaling is involved in the development of different lung cancer-related symptoms. In this review, we summarize recent findings to illustrate the role of P2X receptors in tumor proliferation, progression, metastasis, and lung cancer- related symptoms, providing an outline of potential anti-neoplastic activity of P2X receptor antagonists. Furthermore, compared with opioids, P2X receptor antagonists appear to be innovative therapeutic interventions for managing cancer symptom clusters with fewer side effects.
Highlights
Frontiers in OncologyExtracellular adenosine triphosphatez (ATP) in the tumor microenvironment is associated with tumor cell metabolism, proliferation, and metastasis by driving inflammation and neurotransmission via P2 purinergic signaling
Lung cancer is one of the most common types of cancer, annually causing about 1.8 million deaths worldwide [1]
We speculated that adenosine triphosphatez (ATP) agonists activate various P2X receptors, especially P2X3R, P2X4R, and P2X7R, in other tissues or organs to induce a series of symptoms
Summary
Extracellular ATP in the tumor microenvironment is associated with tumor cell metabolism, proliferation, and metastasis by driving inflammation and neurotransmission via P2 purinergic signaling. ATP gated P2X receptors expressed on tumor cells, immune cells, and neurons play a vital role in modulating tumor development, invasion, progression, and related symptoms. We summarize recent findings to illustrate the role of P2X receptors in tumor proliferation, progression, metastasis, and lung cancer- related symptoms, providing an outline of potential antineoplastic activity of P2X receptor antagonists. Abbreviation: ATP, adenosine triphosphate; BDNF, brain-derived neurotrophic factor; Ca2+, calcium; CNS, central nervous system; CRF, Cancer-related fatigue; CRP, C-reactive protein; HPA, hypothalamic-pituitary-adrenal; NSCLC, non-small cell lung cancer; IL, interleukin; KO, knockout; LPS, lipopolysaccharide; SP, substance P; TNF, tumor necrosis factor; TME, tumor microenvironment; VNUT, vesicular nucleotide transporter
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