Integrin beta‐3 L33P: a new insight into the pathogenesis of chronic oxaliplatin‐induced peripheral neuropathy?

Antonacopoulou, Anna G.; Argyriou, Andreas A.; Scopa, Chrisoula D.; Κοττόρου, Αναστασία; Kominea, Athina; Peroukides, Stavros; Kalofonos, Haralabos P.

doi:10.1111/j.1468-1331.2010.02966.x

Cited by 32 publications

(15 citation statements)

References 25 publications

(36 reference statements)

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“…Genetic variants of alanine glyoxylate aminotransferase (AGXT), an enzyme involved in oxalate metabolism, have been correlated with the severity of oxaliplatin-induced CIPN (Gamelin et al, 2007). Similarly, a polymorphism in the ITGB3 gene—encoding for Integrin B3—was not correlated with the development of oxaliplatin-induced CIPN, although it appeared to be related to the severity of this symptom (Antonacopoulou et al, 2010). This effect may be mediated via the differential activation of the mitogen activated protein kinases MAPK3 and MAPK1 that are induced by these ITGB3 variants, and which may contribute to development of CIPN (Scuteri et al, 2009).…”

Section: The Genetics Of Chemotherapy-induced Peripheral Neuropathymentioning

confidence: 99%

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

Starobova

Vetter

2017

Front. Mol. Neurosci.

458

400

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Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

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Section: The Genetics Of Chemotherapy-induced Peripheral Neuropathymentioning

confidence: 99%

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

Starobova

Vetter

2017

Front. Mol. Neurosci.

458

400

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“…For instance, SNPs in genes involved in the pharmacokinetic, transport, and pharmacodynamic properties of taxanes have been shown to be relevant for TIPN 120,121. Likewise, increased susceptibility to peripheral neurotoxicity after exposure to oxaliplatin and other platinum compounds has been associated with pharmacogenetic variations in genes encoding for drug transporters, detoxification enzymes, genes involved in DNA repair mechanisms, and integrin B3 Leu33Pro polymorphism 122–124…”

Section: Cipn In the Era Of Pharmacogeneticsmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature

Argyriou¹,

Kyritsis²,

Makatsoris³

et al. 2014

CMAR

241

217

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Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In any case, it is acknowledged that the dorsal root ganglia of the primary sensory neurons are the most common neural targets of CIPN. Both the incidence and severity of CIPN are clinically under- and misreported, and it has been demonstrated that scoring CIPN with common toxicity scales is associated with significant inter-observer variability. Only a proportion of chemotherapy-treated patients develop treatment-emergent and persistent CIPN, and to date it has been impossible to predict high-and low-risk subjects even within groups who receive the same drug regimen. This issue has recently been investigated in the context of pharmacogenetic analyses, but these studies have not implemented a proper methodological approach and their results are inconsistent and not really clinically relevant. As such, a stringent approach has to be implemented to validate that information. Another open issue is that, at present, there is insufficient evidence to support the use of any of the already tested chemoprotective agents to prevent or limit CIPN. The results of comprehensive interventions, including clinical, neurophysiological, and pharmacogenetic approaches, are expected to produce a consistent advantage for both doctors and patients and thus allow the registration and analysis of reliable data on the true characteristics of CIPN, eventually leading to potential preventive and therapeutic interventions.

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“…However there is conflicting evidence whether 105 Val polymorphisms of glutathione S-transferase (GSTP1) leads to higher rates of OXIN [29, 30] and there are currently no clinical applications of this basic scientific work. Integrin beta-3 polymorphisms have been shown to be unrelated to the development of OXIN, but may be related to its severity [31]. In a genome-wide analysis of 96 colon cancer patients, a group from South Korea showed a possible connection between OXIN and the DDX18 and NRP2 genes, although the putative mechanism of interaction of these in relation to OXIN is uncertain [32].…”

Section: Incidence Of Oxaliplatin-induced Neuropathymentioning

confidence: 99%

Oxaliplatin-Induced Neuropathy in Colorectal Cancer

Weickhardt

Wells

Messersmith

2011

Journal of Oncology

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Oxaliplatin use in palliative and adjuvant treatment of colon cancer is frequently limited by cumulative neurotoxicity, leading to reduced quality of life and decreased dose. The mechanism of this neurotoxicity is unclear, but may relate to neuronal voltage-gated sodium channels involving calcium chelation by a metabolite of the drug. Various preventative measures have been tested to reduce the incidence of neurotoxicity, including calcium and magnesium infusions, dose interruption of the drug, and prophylactic neuromodulatory agents. Despite the promising efficacy of these measures, they are not universally accepted. Less is known about the best way to treat established neurotoxicity, which is permanent in some patients, although venlafaxine has shown promise in small clinical trials. This paper analyzes the extent, cause and risk factors for neuropathy, and the potential preventative and therapeutic treatments for oxaliplatin-induced neuropathy.

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Integrin beta‐3 L33P: a new insight into the pathogenesis of chronic oxaliplatin‐induced peripheral neuropathy?

Abstract: The ITGB3 L33P seems to be unrelated to the development of OXLIPN, but it appears to be related to its severity.

Cited by 32 publications

References 25 publications

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature

Oxaliplatin-Induced Neuropathy in Colorectal Cancer

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