Treatment for metastatic malignant melanoma: Old drugs and new strategies

Mouawad, Roger; Sébert, Marie; Michels, Judith; Bloch, J.S.; Spano, Jean‐Philippe; Khayat, David

doi:10.1016/j.critrevonc.2009.08.005

Cited by 109 publications

(119 citation statements)

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“…Metastatic melanoma is difficult to treat as standard chemotherapy [highdose interleukin (IL)-2 and dacarbazine] cannot significantly improve the overall survival (OS; ref. 2). Targeted therapeutic agents have shown promising clinical efficacy, such as BRAF inhibitors (e.g., vemurafenib and dabrafenib; refs.…”

Section: Introductionmentioning

confidence: 99%

Large-scale Analysis of PDGFRA Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib

Dai

Kong

et al. 2013

Clinical Cancer Research

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Purpose: Platelet-derived growth factor receptor a (PDGFRA) is a target for tyrosine kinase inhibitor (TKI)-based targeted therapy. Dysregulation of PDGFRA has been reported in many cancers. However, PDGFRA mutations in melanomas have not been well studied. We analyzed the genetic mutations of PDGFRA in Chinese patients with melanoma and determined the inhibitory potency of TKIs, such as imatinib and crenolanib, on mutant PDGFRA.Experimental Design: Of note, 351 melanoma tissue samples were examined for genetic mutations in exons 12, 14, and 18 of PDGFRA. Activities of mutations in response to imatinib and crenolanib were analyzed by Western blotting of tyrosine-phosphorylated PDGFRA and cell proliferation assays.Results: PDGFRA mutations were observed in 4.6% (16 of 351) of melanomas, and these mutations were mainly detected in acral and mucosal melanomas. PDGFRA mutations seem to be mutually exclusive with KIT mutations, but may coexist with BRAF and NRAS mutations. The genetic mutations of PDGFRA were unrelated to the age, thickness, and ulceration status of primary melanomas. Thirteen mutations were not reported before, and five (P577S, V658A, R841K, H845Y, and G853D) of them resulted in strong autophosphorylation of PDGFRA. Crenolanib showed higher potency than imatinib in inhibiting the kinase activity of PDGFRA. Except that V658A mutation was imatinib-resistant, all the other mutations were sensitive to both imatinib and crenolanib.Conclusions: PDGFRA mutations are detected in a small population of melanoma patients. Our study suggests that patients with melanoma harboring certain PDGFRA mutations may benefit from imatinib and crenolanib treatment.

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Section: Introductionmentioning

confidence: 99%

Large-scale Analysis of PDGFRA Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib

Dai

Kong

et al. 2013

Clinical Cancer Research

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“…1 With early diagnosis and adequate surgical treatment of primary tumors (Stage I patients), the 5-year survival rate is 495%. 2 However, once melanoma has metastasized to distant sites, life expectancy dramatically declines, with 1-year survival rate of 33% for patients with Stage IV metastatic disease.…”

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confidence: 99%

Maspin expression and melanoma progression: a matter of sub-cellular localization

et al. 2014

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Maspin, a member of the serpin family of protease inhibitors, is involved in key processes of cancer progression. Its biological activity seems to be cancer and compartment specific, with the protein acting either as a suppressor or as a tumor promoter in different cancer types. Characterization of maspin expression and its sub-cellular localization in melanoma is missing, hence, we aim to investigate its possible association with melanoma prognostic factors and disease progression. Nuclear and cytoplasmic maspin expression were evaluated on 60 nevi, 152 primary lesions, and 106 melanoma metastases using tissue microarrays and immunohistochemistry. The association between maspin immunoreactivity and patient's clinic-pathological features was evaluated. Multivariate logistic models and survival analyses were performed for maspin expression in primary melanomas. Nuclear maspin was detected in 8% nevi, 49% primary melanomas, and 28% metastases, whereas cytoplasmic maspin in 12% nevi, 18% primary lesions, and 9% metastases. In univariate analysis, nuclear maspin expression in primary melanomas was significantly associated with melanoma prognostic factors (nodular histotype, tumor thickness, mitotic rate, and ulceration) and disease stage, whereas cytoplasmic maspin was observed at higher frequency in thin superficial spreading melanomas, without mitosis. In multivariate analysis, nuclear maspin remained significantly associated with risk of developing a tumor prone to disease progression and, accordingly, with significantly shorter disease-free and overall survival. In this study, maspin was expressed at highest frequency in primary lesions and when expressed in the nuclei, was significantly associated with poor prognostic markers, melanoma recurrence, and worse survival. The present study suggests a tumor-suppressive effect of cytoplasmic maspin and a tumor-promoting effect of nuclear maspin, which open the discussion on its potential use in cancer therapy. Modern Pathology (2014) 27, 412-419; doi:10.1038/modpathol.2013.157; published online 13 September 2013Keywords: biomarker; maspin; melanoma; tissue microarrays Melanoma is a malignant neoplasm that originates from melanocytes and it is characterized by frequent local recurrence, early metastasis, and refractoriness to chemotherapy and biological treatment. 1 With early diagnosis and adequate surgical treatment of primary tumors (Stage I patients), the 5-year survival rate is 495%. 2 However, once melanoma has metastasized to distant sites, life expectancy dramatically declines, with 1-year survival rate of 33% for patients with Stage IV metastatic disease. 2 Primary tumor thickness, ulceration, and mitotic rate, together with the presence of lymph node and systemic metastases, are the histopathologic criteria used for melanoma staging to predict disease outcome in terms of life expectancy and survival rates. 2 However, a significant minority of melanomas contravenes these conventional parameters and displays unpredictable clinical behavior. Furthermore, lack of...

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“…Hence, the reader is referred to review articles on immunological melanoma therapy for further reading (Finn 2008, Mouawad et al 2010, Gyorki et al 2013). …”

Section: Immunological Melanoma Therapiesmentioning

confidence: 99%

Prospect for immunological therapies of the equine malignant melanoma

Cavalleri¹,

Mählmann²,

Schuberth³

et al. 2015

PHK

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Summary: Although equine melanocytic neoplasms occur frequently, at least in grey horses, their existence is neglected frequently, despite their potentially severe clinical consequences. Immune-based therapies have been investigated in human metastatic melanoma and offer encouraging results. Researchers have recently begun to explore the immunological approach in equine malignant melanoma (EMM) with some success. Therefore, this review aims at giving a short overview of the nature of EMM and providing insight into the immunological basis of melanocytic neoplasms in general. Equine malignant melanoma is a true neoplasm with a genetic basis. Initially they show a slow invasive growth, but they have the potential to metastasize. EMM and human malignant melanomas share various common histopathologic features. For the immune system eradication of the tumor is a challenge. Although solid tumors are often infiltrated with immune cells, they usually do not induce a significant tumor remission. The antitumoral immune response depends on factors of the innate immune system interacting in a coordinated fashion with the adaptive immune system. Antigen-presenting cells, neutrophilic granulocytes, and lymphoid cells may elicit antitumoral effects. This innate response precedes a downstream antigen-specific response. In the tumor microenvironment of solid tumors immune suppressive factors can induce immune escape mechanisms of the tumors. Immunological therapies of EMM include blockage of histamine 2 receptors on melanoma cells and lymphocytes, cancer vaccines and gene therapeutic approaches. This article focuses on the immunological therapeutic approach of EMM and gives an outlook on future implications.

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Treatment for metastatic malignant melanoma: Old drugs and new strategies

Cited by 109 publications

References 100 publications

Large-scale Analysis of PDGFRA Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib

Large-scale Analysis of PDGFRA Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib

Maspin expression and melanoma progression: a matter of sub-cellular localization

Prospect for immunological therapies of the equine malignant melanoma

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