Phase II study of intravenous adenosine 5'-triphosphate in patients with previously untreated stage IIIB and Stage IV non-small cell lung cancer

Haskell, Charles M.; Mendoza, Evelyn; Pisters, Katherine M.W.; Fossella, Frank V.; Figlin, Robert A.

doi:10.1023/a:1006018610986

Cited by 47 publications

(6 citation statements)

References 15 publications

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“…It has also been reported from several studies that intravenous infusions of ATP in pre-terminal cancer patients produces a common adverse effect in a large proportion of patients: chest discomfort/pain, dyspnea and the urge to take a deep breath (Haskell et al, 1998; Beijer et al, 2007). Some of these effects had been predicted based on a small number of preclinical evaluations examining ATP activation of canine pulmonary vagal afferents (Hurt et al, 1994) as well as participation in induction of cough in guinea pigs in response to tussive agents (Kamei et al, 2005; Kamei and Takahashi, 2006).…”

Section: The Sensitizing Property Of Atpmentioning

confidence: 98%

The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders

Ford

Undem

2013

Front. Cell. Neurosci.

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A sensory role for ATP was proposed long before general acceptance of its extracellular role. ATP activates and sensitizes signal transmission at multiple sites along the sensory axis, across multiple synapses. P2X and P2Y receptors mediate ATP modulation of sensory pathways and participate in dysregulation, where ATP action directly on primary afferent neurons (PANs), linking receptive field to CNS, has received much attention. Many PANs, especially C-fibers, are activated by ATP, via P2X3-containing trimers. P2X3 knock-out mice and knock-down in rats led to reduced nocifensive activity and visceral reflexes, suggesting that antagonism may offer benefit in sensory disorders. Recently, drug-like P2X3 antagonists, active in a many inflammatory and visceral pain models, have emerged. Significantly, these compounds have no overt CNS action and are inactive versus acute nociception. Selectively targeting ATP sensitization of PANs may lead to therapies that block inappropriate chronic signals at their source, decreasing drivers of peripheral and central wind-up, yet leaving defensive nociceptive and brain functions unperturbed. This article reviews this evidence, focusing on how ATP sensitization of PANs in visceral “hollow” organs primes them to chronic discomfort, irritation and pain (symptoms) as well as exacerbated autonomic reflexes (signs), and how the use of isolated organ-nerve preparations has revealed this mechanism. Urinary and airways systems share many features: dependence on continuous afferent traffic to brainstem centers to coordinate efferent autonomic outflow; loss of descending inhibitory influence in functional and sensory disorders; dependence on ATP in mediating sensory responses to diverse mechanical and chemical stimuli; a mechanistically overlapping array of existing medicines for pathological conditions. These similarities may also play out in terms of future treatment of signs and symptoms, in the potential for benefit of P2X3 antagonists.

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Section: The Sensitizing Property Of Atpmentioning

confidence: 98%

The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders

Ford

Undem

2013

Front. Cell. Neurosci.

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“… 101 , 104 Furthermore, the effect of ATP infusion in patients with advanced lung cancer has proven the potential of ATP, which might become an anti-cancer agent in the future. 105 , 106 , 107 , 108 However, larger studies are required in order to verify these findings.…”

Section: Purinergic Receptorsmentioning

confidence: 99%

Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells

2015

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Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca2+ influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca2+ homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression.

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“…Inhaling ATP and adenosine induced dyspnea in subjects with asthma (123) and COPD (124). Additionally, intravenous injection of adenosine induced distressing symptoms such as dyspnea, hyperventilation, urge for deep breathing, and chest tightness in healthy volunteers (125), and pre-terminal cancer patients (45,126). Taken together, extracellular ATP is likely to give rise to dyspnea, and thus may be a potential target for the treatment of dyspnea.…”

Section: Cancer-related Dyspneamentioning

confidence: 99%

P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer — A Mini Review

et al. 2021

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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.

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Phase II study of intravenous adenosine 5'-triphosphate in patients with previously untreated stage IIIB and Stage IV non-small cell lung cancer

Cited by 47 publications

References 15 publications

The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders

The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders

Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells

P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer — A Mini Review

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