A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma

Suarez‐Kelly, Lorena P.; Levine, Kala; Olencki, Thomas; Campo, Sara E. Martin del; Streacker, Elizabeth A.; Brooks, Taylor; Karpa, Volodymyr; Markowitz, Joseph; Bingman, Anissa; Geyer, Susan; Kendra, Kari; Carson, William E.

doi:10.1007/s00262-019-02308-w

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…However, some reports explored the impact of STAT3 versus STAT1, as well as the non-canonical involvement of MAPKs, SIRT2, and SLFN5. STAT1 phosphorylation and the induced expression of various ISGs such as OASL and ISG15 have commonly been used as indicators of a type I IFN response (19,27,28,34,35). In a study on cervical cancer, the importance of IFN-inducible activation of STAT1 and STAT2 was demonstrated through the use of STAT1 and STAT2 knockout human HeLa cells, yet the STAT3 knockout did not have any effect on ISGs (24).…”

Section: Canonical and Non-canonical Ifn Signaling In Malignanciesmentioning

confidence: 99%

“…A pilot study looked at the potential of decreasing the dose of IFN-a2b for the treatment of melanoma over the course of an 11-month treatment period. Despite the dose reduction, p-STAT1 levels were induced at comparable levels throughout the 11 months, and the IFN was well-tolerated (28). An alternative strategy has been to stimulate the endogenous type I IFN response in immune cells.…”

Section: Canonical and Non-canonical Ifn Signaling In Malignanciesmentioning

confidence: 99%

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Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

et al. 2020

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For several decades there has been accumulating evidence implicating type I interferons (IFNs) as key elements of the immune response. Therapeutic approaches incorporating different recombinant type I IFN proteins have been successfully employed to treat a diverse group of diseases with significant and positive outcomes. The biological activities of type I IFNs are consequences of signaling events occurring in the cytoplasm and nucleus of cells. Biochemical events involving JAK/STAT proteins that control transcriptional activation of IFN-stimulated genes (ISGs) were the first to be identified and are referred to as “canonical” signaling. Subsequent identification of JAK/STAT-independent signaling pathways, critical for ISG transcription and/or mRNA translation, are denoted as “non-canonical” or “non-classical” pathways. In this review, we summarize these signaling cascades and discuss recent developments in the field, specifically as they relate to the biological and clinical implications of engagement of both canonical and non-canonical pathways.

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Section: Canonical and Non-canonical Ifn Signaling In Malignanciesmentioning

confidence: 99%

Section: Canonical and Non-canonical Ifn Signaling In Malignanciesmentioning

confidence: 99%

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

et al. 2020

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“…Alternatively, the CyKs are produced at tumor site, as is type I IFN or IFN-γ, by stimulating immune cells with specific up-regulators as toll-like receptor agonists [ 189 ]. For CM, the FDA approved in trials immunotherapies include so far: (a) interferon (IFN) α-2b [ 190 ], (b) polyethylene glycol(PEG)interferon α 2b (PEG-IFN), a combination of IFN α -2b with PEG ) [ 191 ] and (c) IL-2 [ 192 ].…”

Section: Interleukin 8—a Major Key-player In CM Pathogenesismentioning

confidence: 99%

Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy—An Integrated View into Other Neoplasms and Chemokine Networks

Filimon

Preda

Boloca

et al. 2021

Cells

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Cutaneous melanoma accounts for only about 7% of skin cancers but is causing almost 90% of deaths. Melanoma cells have a distinct repertoire of mutations from other cancers, a high plasticity and degree of mimicry toward vascular phenotype, stemness markers, versatility in evading and suppress host immune control. They exert a significant influence on immune, endothelial and various stromal cells which form tumor microenvironment. The metastatic stage, the leading cause of mortality in this neoplasm, is the outcome of a complex, still poorly understood, cross-talk between tumor and other cell phenotypes. There is accumulating evidence that Interleukin-8 (IL-8) is emblematic for advanced melanomas. This work aimed to present an updated status of IL-8 in melanoma tumor cellular complexity, through a comprehensive analysis including data from other chemokines and neoplasms. The multiple processes and mechanisms surveyed here demonstrate that IL-8 operates following orchestrated programs within signaling webs in melanoma, stromal and vascular cells. Importantly, the yet unknown molecularity regulating IL-8 impact on cells of the immune system could be exploited to overturn tumor fate. The molecular and cellular targets of IL-8 should be brought into the attention of even more intense scientific exploration and valorization in the therapeutical management of melanoma.

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“…2 . In vivo and in vitro, IFN-α2b can activate the JAK-STAT pathway (also known as IFN-I pathway) [ 21 ]. As mentioned above, IFN-α2b can bind to IFNARs.…”

Section: Introductionmentioning

confidence: 99%

“…IFN-α2b can induce a state of autoimmunity that is beneficial to the prognosis, which can be detected by the measurement of autoantibodies [ 247 ]. Some components of the IFN-I pathway, such as p-STAT1 and ISGs, can also indicate the pharmacological response to IFN-α2b [ 21 ]. In a joint laboratory and clinical trial (E1690), modulation of intercellular adhesion molecule 1 (ICAM1) was observed by flow cytometry upon IFN-α2b treatment [ 248 ].…”

Section: Introductionmentioning

confidence: 99%

Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow

Xiong

Wang

et al. 2022

Biomark Res

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Interferon-α2b (IFN-α2b) is a highly active cytokine that belongs to the interferon-α (IFN-α) family. IFN-α2b has beneficial antiviral, antitumour, antiparasitic and immunomodulatory activities. Direct and indirect antiproliferative effects of IFN-α2b have been found to occur via multiple pathways, mainly the JAK-STAT pathway, in certain cancers. This article reviews mechanistic studies and clinical trials on IFN-α2b. Potential regulators of the function of IFN-α2b were also reviewed, which could be utilized to relieve the poor response to IFN-α2b. IFN-α2b can function not only by enhancing the systematic immune response but also by directly killing tumour cells. Different parts of JAK-STAT pathway activated by IFN-α2b, such as interferon alpha and beta receptors (IFNARs), Janus kinases (JAKs) and IFN‐stimulated gene factor 3 (ISGF3), might serve as potential target for enhancing the pharmacological action of IFN-α2b. Despite some issues that remain to be solved, based on current evidence, IFN-α2b can inhibit disease progression and improve the survival of patients with certain types of malignant tumours. More efforts should be made to address potential adverse effects and complications.

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A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma

Cited by 7 publications

References 36 publications

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy—An Integrated View into Other Neoplasms and Chemokine Networks

Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow

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