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The role for chemotherapy in the modern management of melanoma.

ABSTRACT: The treatment of malignant melanoma has changed beyond recognition in the last 7 years. Where previously single agent dacarbazine was often the only treatment used for advanced disease, now there are potentially multiple lines of treatment, based on immunotherapy and targeted treatment options, either as monotherapy or in combination. In this brave new world the question arises, does chemotherapy still have any relevance in the modern management of melanoma? In this review, we summarize the various chemotherapeutic options that have been trialled in melanoma to date, and discuss the role chemotherapy may still play in treating melanoma, potentially in combination with more novel agents, or in certain subtypes of melanoma.

SUBMITTER: Gupta A

PROVIDER: S-EPMC6094602 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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The role for chemotherapy in the modern management of melanoma.

Gupta Avinash A Gomes Fabio F Lorigan Paul P

Melanoma management 20170519 2

The treatment of malignant melanoma has changed beyond recognition in the last 7 years. Where previously single agent dacarbazine was often the only treatment used for advanced disease, now there are potentially multiple lines of treatment, based on immunotherapy and targeted treatment options, either as monotherapy or in combination. In this brave new world the question arises, does chemotherapy still have any relevance in the modern management of melanoma? In this review, we summarize the vari ...[more]

PMID: 30190915

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Project description:Introduction. Retinoblastoma is the most common primary intraocular neoplasm in children. With the advances in medicine, the armamentarium of available treatment modalities has grown. Intraarterial chemotherapy is a relatively new treatment method with promising outcomes. The purpose of this literature review is to evaluate its role in the management of retinoblastoma.MethodsA systematic online search was conducted using Ovid Embase and Ovid Medline. The final results included 23 studies. The studies were published between 2011 and 2019. The studies evaluated the technical success rate of IAC, globe salvage rate, and ocular and systemic complications, as well as the occurrence of deaths, metastasis, and secondary neoplasms. In total, 1827 eyes with retinoblastoma were analysed. The follow-up was between 0 and 252 months.ResultsOverall globe retention rate ranged from 30% to 100%. Sixteen out of 23 studies reported ocular salvage between 60 and 80%. Eyelid oedema and erythema were the most commonly reported ocular complications following IAC. The most common systemic complications included nausea, vomiting, and neutropenia. Metastases and deaths were reported in 6 out of 23 studies. Three studies reported the development of secondary neoplasms. The technical success rate of IAC procedure ranged from 91% to 100%. Discussion. The studies have shown that IAC is a safe and effective treatment for advanced retinoblastoma, especially group D. It allows to save the globe without compromising patients' survival. Local and systemic complications are acceptable. The role of IAC in less advanced tumours is yet to be established. Future work should focus on conducting larger prospective studies with longer follow-up. Multiple novel therapies for the management of retinoblastoma are currently being tested, including angiogenic inhibitors and targeted agents. The results seem to be promising. Future advances require a further in-depth understanding of unique genetics of retinoblastoma and complex interactions between tumour cells and their microenvironment.

Project description:Ultraviolet B (UVB), in addition to having carcinogenic activity, is required for the production of vitamin D3 (D3) in the skin which supplies >90% of the body's requirement. Vitamin D is activated through hydroxylation by 25-hydroxylases (CYP2R1 or CYP27A1) and 1α-hydroxylase (CYP27B1) to produce 1,25(OH)2D3, or through the action of CYP11A1 to produce mono-di- and trihydroxy-D3 products that can be further modified by CYP27B1, CYP27A1, and CYP24A1. The active forms of D3, in addition to regulating calcium metabolism, exert pleiotropic activities, which include anticarcinogenic and anti-melanoma effects in experimental models, with photoprotection against UVB-induced damage. These diverse effects are mediated through an interaction with the vitamin D receptor (VDR) and/or as most recently demonstrated through action on retinoic acid orphan receptors (ROR)α and RORγ. With respect to melanoma, low levels of 25(OH)D are associated with thicker tumors and reduced patient survival. Furthermore, single-nucleotide polymorphisms of VDR and the vitamin D-binding protein (VDP) genes affect melanomagenesis or disease outcome. Clinicopathological analyses have shown positive correlation between low or undetectable expression of VDR and/or CYP27B1 in melanoma with tumor progression and shorter overall (OS) and disease-free survival (DFS) times. Paradoxically, this correlation was reversed for CYP24A1 (inactivating 24-hydroxylase), indicating that this enzyme, while inactivating 1,25(OH)2D3, can activate other forms of D3 that are products of the non-canonical pathway initiated by CYP11A1. An inverse correlation has been found between the levels of RORα and RORγ expression and melanoma progression and disease outcome. Therefore, we propose that defects in vitamin D signaling including D3 activation/inactivation, and the expression and activity of the corresponding receptors, affect melanoma progression and the outcome of the disease. The existence of multiple bioactive forms of D3 and alternative receptors affecting the behavior of melanoma should be taken into consideration when applying vitamin D management for melanoma therapy.

Dataset Information

The role for chemotherapy in the modern management of melanoma.

Publications

The role for chemotherapy in the modern management of melanoma.

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