Advances in the treatment of melanoma

Lacy, Katie E.; Karagiannis, Sophia N.; Nestle, Frank O.

doi:10.7861/clinmedicine.12-2-168

Cited by 13 publications

(9 citation statements)

References 14 publications

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“…The contribution of different immune cell components to cutaneous immune responses has been thoroughly investigated in recent years [5][6][7][8][9], and these efforts have led to significant advances in the treatment of inflammatory skin conditions and skin tumors, including the use of immunobiological agents developed as a result of an improved understanding of the cutaneous immune system. Of particular note, recent developments in the treatment of metastatic melanoma aimed at stimulating the antitumor immune response have offered improved survival for patients where therapeutic options were previously very limited [10].…”

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confidence: 99%

Revisiting the role of B cells in skin immune surveillance

Egbuniwe

Karagiannis

Nestle

et al. 2015

Trends in Immunology

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Whereas our understanding of the skin immune system has increased exponentially in recent years, the role of B cells in cutaneous immunity remains poorly defined. Recent studies have revealed the presence of B cells within lymphocytic infiltrates in chronic inflammatory skin diseases and cutaneous malignancies including melanoma, and have examined their functional significance in these settings. We review these findings and discuss them in the context of the current understanding of the role of B cells in normal skin physiology, as well as in both animal and human models of skin pathology. We integrate these findings into a model of cutaneous immunity wherein crosstalk between B cells and other skin-resident immune cells plays a central role in skin immune homeostasis.

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confidence: 99%

Revisiting the role of B cells in skin immune surveillance

Egbuniwe

Karagiannis

Nestle

et al. 2015

Trends in Immunology

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“…The majority (~90%) of patients with early detected melanoma are curable; however, the efficiency of clinical drugs in the treatment of patients with advanced metastatic melanoma is <20% (2), and the 5-year survival rate is <5%, with a median survival time of only 2-8 months (3,4). Numerous studies have confirmed that the poor prognosis of malignant melanoma is primarily attributable to the high incidence of distant metastasis and a strong capacity for invasion (5)(6)(7). Therefore, the development of more effective therapies for the inhibition of metastasis presents a challenge for the treatment of malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

Zhang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Euphorbia fischeriana Steud, a traditional Chinese medicine, has been shown to inhibit the growth of various cancers by the induction of apoptosis and cell cycle arrest. The purpose of the present study was to investigate the association between the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and the inhibitory effect of Euphorbia fischeriana Steud on the growth and metastasis of melanoma B16 cells in vitro, and the underlying mechanisms. MTT assay results indicated that Euphorbia fischeriana Steud inhibited the growth of B16 cells in a time-and dose-dependent manner. Flow cytometric analysis revealed that Euphorbia fischeriana Steud markedly induced apoptosis of the B16 cells, with arrest at the G0/G1 phase of the cell cycle. In addition, in a Transwell assay Euphorbia fischeriana Steud significantly suppressed the migration of B16 cells. Western blot analysis revealed that the expression levels of phosphatase and tensin homolog (PTEN) were upregulated, and the phosphorylation of Akt was downregulated, which resulted in inhibition of the PI3K/Akt signaling pathway and the eventual suppression of its downstream targets, such as matrix metalloproteinase-2 mRNA, in B16 cells. The results demonstrated that Euphorbia fischeriana Steud inhibited the growth and migration of B16 cells, possibly via modulation of the PI3K/Akt signaling pathway and upregulation of PTEN expression levels, in addition to downregulation of p-Akt expression. The aforementioned findings suggest that Euphorbia fischeriana Steud may have broad therapeutic applications in the treatment of malignant melanoma. IntroductionMalignant melanoma has become a frequently occurring malignancy with an annual increase of ~3% (1). The majority (~90%) of patients with early detected melanoma are curable; however, the efficiency of clinical drugs in the treatment of patients with advanced metastatic melanoma is <20% (2), and the 5-year survival rate is <5%, with a median survival time of only 2-8 months (3,4). Numerous studies have confirmed that the poor prognosis of malignant melanoma is primarily attributable to the high incidence of distant metastasis and a strong capacity for invasion (5-7). Therefore, the development of more effective therapies for the inhibition of metastasis presents a challenge for the treatment of malignant melanoma.Chemotherapy has a significant role in the treatment of cancer. However, the majority of chemotherapy drugs also destroy normal cells, leading to adverse effects (8). Therefore, the identification of natural compounds with a wide range of anticancer activities, high selectivity for the destruction of cancer cells and low toxicity of normal cells is of importance in cancer research. Euphorbia fischeriana Steud (also known as lang-du), a herbaceous plant used in traditional Chinese medicine (TCM), has demonstrated inhibitory effects through its capacity to induce apoptosis, suppress growth and cause cell cycle arrest when assessed within several cancer cell lines, including leukemia a...

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“…In the UK, in 2016, almost 14,000 new cases of melanoma were diagnosed [3]. Approximately 9% of all melanoma patients are diagnosed with advanced melanoma (stage III or stage IV) [4], and approximately 20% of people treated for early stage primary melanoma progress to an advanced stage [7]. The 5-year survival rate for stage IIIB melanoma is around 60%, although the survival rate at 1-year for stage IV disease may be as low as 33% [4].…”

Section: Decision Problemmentioning

confidence: 99%

Encorafenib with Binimetinib for the Treatment of Patients with BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Houten

Greenhalgh

Mahon

et al. 2020

PharmacoEconomics Open

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As part of the Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited Pierre Fabre to submit evidence for the clinical and cost-effectiveness of encorafenib with binimetinib (Enco + Bini) versus dabrafenib with trametinib (Dab + Tram) as a first-line treatment for advanced (unresectable or metastatic) BRAF V600 mutation-positive melanoma. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned as the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission (CS), and the Appraisal Committee's (AC's) final decision. The main clinical evidence in the CS was derived from the COLUMBUS trial and focused on the efficacy of Enco + Bini (encorafenib 450 mg per day plus binimetinib 45 mg twice daily) compared to vemurafenib. The company conducted network meta-analyses (NMAs) to indirectly estimate the relative effects of progression-free survival (PFS), overall survival (OS), adverse events (AEs) and health-related quality of life (HRQoL) for Enco + Bini versus Dab + Tram. None of the results from the NMAs demonstrated a statistically significant difference between the treatment regimens for any outcomes. The ERG advised caution when interpreting the results from the company's NMAs due to limitations relating to the methods. The ERG considered that use of the OS and PFS hazard ratios (HRs) generated by the company's NMAs to model the relative effectiveness of Enco + Bini versus Dab + Tram in the company model was inappropriate as these estimates were not statistically significantly different. The ERG amended the company's economic model to include estimates of equivalent efficacy, safety and HRQoL for Enco + Bini and Dab + Tram. The ERG considered use of different estimates of relative dose intensity to be inappropriate and used the same estimate for both drug combinations. The ERG also concluded that as only the prices of drug combinations were different, a cost comparison was an appropriate method of economic analysis. Using this approach (combined with confidential discounted drug prices for Enco + Bini and Dab + Tram), treatment with Enco + Bini was more cost effective than treatment with Dab + Tram. The AC raised concerns that an absence of evidence of a difference in outcomes between Enco + Bini and Dab + Tram did not constitute evidence of absence. However, as the numerical differences in outcomes generated by the company's networks were small, the AC did not have a preferred approach and considered that both the company's and the ERG's methods of incorporating outcome estimates into the economic model were suitable for decision making. The NICE AC recommended Enco + Bini as a first-line treatment for unresectable or metastatic melanoma with a BRAF V600 mutation.

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Advances in the treatment of melanoma

Cited by 13 publications

References 14 publications

Revisiting the role of B cells in skin immune surveillance

Revisiting the role of B cells in skin immune surveillance

Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

Encorafenib with Binimetinib for the Treatment of Patients with BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

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