Oxaliplatin-Induced Neuropathy: Genetic and Epigenetic Profile to Better Understand How to Ameliorate This Side Effect

Branca, Jacopo Junio Valerio; Carrino, Donatello; Gulisano, Massimo; Ghelardini, Carla; Mannelli, Lorenzo Di Cesare; Pacini, Alessandra

doi:10.3389/fmolb.2021.643824

Cited by 29 publications

(19 citation statements)

References 90 publications

(76 reference statements)

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“…One of the main issues in the delivery of chemotherapeutics for cancer treatment is the onset of off-site side effects, which can cause a wide spectrum of complications, such as infections, neuropathies, cytopenias, nephrotoxicity, cardiotoxicity and hepatotoxicity [95][96][97][98]. NP-based delivery systems are utilized in oncology primarily to reduce the severity of these side effects, improving drug accumulation at the tumor site.…”

Section: Fn-based Nps For Cancer Treatment In Preclinical Modelsmentioning

confidence: 99%

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

et al. 2021

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Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One of the main favorable characteristics of FNs is their intrinsic targeting efficiency toward the Transferrin Receptor 1, which is overexpressed in many tumors. Furthermore, genetic manipulation can be employed to introduce novel variants that are able to improve the loading capacity, targeting capabilities and bio-availability of this versatile drug delivery system. In this review, we discuss the main characteristics of FN and the most recent applications of this promising nanotechnology in the field of oncology with a particular emphasis on the imaging and treatment of solid tumors.

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Section: Fn-based Nps For Cancer Treatment In Preclinical Modelsmentioning

confidence: 99%

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

et al. 2021

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“…Since MC38 tumor growth was associated with systemic reductions in IENF density, we investigated wellestablished indicators of neuronal damage at the level of the DRG: elevated macrophage density and increased expression of ATF-3 [52][53][54]. We did not observe any significant changes in lumbar DRG CD68 density or ATF-3 expression in samples from tumor-bearing vs control mice (Fig.…”

Section: Mc38 Tumor Does Not Change Neuronal Damage- or Macrophage Ma...mentioning

confidence: 94%

Sensory neuron dysfunction in orthotopic mouse models of colon cancer

Balogh

Zhang

Gaffney

et al. 2022

J Neuroinflammation

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Reports of neurological sequelae related to colon cancer are largely restricted to rare instances of paraneoplastic syndromes, due to autoimmune reactions. Systemic inflammation associated with tumor development influences sensory neuron function in other disease models, though the extent to which this occurs in colorectal cancer is unknown. We induced orthotopic colorectal cancer via orthotopic injection of two colorectal cancer cell lines (MC38 and CT26) in two different mouse strains (C57BL/6 and Balb/c, respectively). Behavioral tests of pain sensitivity and activity did not detect significant alterations in sensory sensitivity or diminished well-being throughout tumor development. However, immunohistochemistry revealed widespread reductions in intraepidermal nerve fiber density in the skin of tumor-bearing mice. Though loss of nerve fiber density was not associated with increased expression of cell injury markers in dorsal root ganglia, lumbar dorsal root ganglia neurons of tumor-bearing animals showed deficits in mitochondrial function. These neurons also had reduced cytosolic calcium levels in live-cell imaging and reduced spontaneous activity in multi-electrode array analysis. Bulk RNA sequencing of DRGs from tumor-bearing mice detected activation of gene expression pathways associated with elevated cytokine and chemokine signaling, including CXCL10. This is consistent with the detection of CXCL10 (and numerous other cytokines, chemokines and growth factors) in MC38 and CT26 cell-conditioned media, and the serum of tumor-bearing mice. Our study demonstrates in a pre-clinical setting that colon cancer is associated with latent sensory neuron dysfunction and implicates cytokine/chemokine signaling in this process. These findings may have implications for determining risk factors and treatment responsiveness related to neuropathy in colorectal cancer.

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“…Oxaliplatin results in peripheral neuropathy and mild to moderate vascular pain at the site of injection. The exact reason of vascular pain is not clear; however, peripheral neuropathy occurs due to the destruction of sensory neurons through the binding of the drug to the sensory neuron DNA [49].…”

Section: Alkylating Agentsmentioning

confidence: 99%

Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile

Basak

Arrighi

Darwiche

et al. 2021

Life

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The inception of cancer treatment with chemotherapeutics began in the 1940s with nitrogen mustards that were initially employed as weapons in World War II. Since then, treatment options for different malignancies have evolved over the period of last seventy years. Until the late 1990s, all the chemotherapeutic agents were small molecule chemicals with a highly nonspecific and severe toxicity spectrum. With the landmark approval of rituximab in 1997, a new horizon has opened up for numerous therapeutic antibodies in solid and hematological cancers. Although this transition to large molecules improved the survival and quality of life of cancer patients, this has also coincided with the change in adverse effect patterns. Typically, the anticancer agents are fraught with multifarious adverse effects that negatively impact different organs of cancer patients, which ultimately aggravate their sufferings. In contrast to the small molecules, anticancer antibodies are more targeted toward cancer signaling pathways and exhibit fewer side effects than traditional small molecule chemotherapy treatments. Nevertheless, the interference with the immune system triggers serious inflammation- and infection-related adverse effects. The differences in drug disposition and interaction with human basal pathways contribute to this paradigm shift in adverse effect profile. It is critical that healthcare team members gain a thorough insight of the adverse effect differences between the agents discovered during the last twenty-five years and before. In this review, we summarized the general mechanisms and adverse effects of small and large molecule anticancer drugs that would further our understanding on the toxicity patterns of chemotherapeutic regimens.

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Oxaliplatin-Induced Neuropathy: Genetic and Epigenetic Profile to Better Understand How to Ameliorate This Side Effect

Cited by 29 publications

References 90 publications

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

Sensory neuron dysfunction in orthotopic mouse models of colon cancer

Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile

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