Chemotherapy and biologic therapies for melanoma: do they work?

Jilaveanu, Lucia B.; Aziz, Saadia A.; Kluger, Harriet M.

doi:10.1016/j.clindermatol.2008.09.020

Cited by 86 publications

(67 citation statements)

References 99 publications

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“…In its early stages, melanoma is highly curable with surgery, but approximately one third of all patients with melanoma experience disease recurrence and metastasis; once metastasis has occurred, it is often fatal (2). Patients whose tumors contain a BRAF gene mutation may benefit from treatment with mitogen-activated protein kinase pathway inhibitors; however, the development of resistance through multiple distinct mechanisms is a major problem (3).…”

Section: Introductionmentioning

confidence: 99%

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

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Section: Introductionmentioning

confidence: 99%

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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“…This type of skin cancer has traditionally been difficult to treat because of its known universal resistance to standard chemotherapy [2]. Early stage disease can often be cured by surgery; however, unresectable cancer must be treated with systemic therapy.…”

Section: Introductionmentioning

confidence: 99%

The curcumin analog DM-1 induces apoptotic cell death in melanoma

et al. 2013

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SummaryThe main difficulty in the successful treatment of metastatic melanoma is that this type of cancer is known to be resistant to chemotherapy. Chemotherapy remains the treatment of choice and dacarbazine (DTIC) is the best standard treatment. The DM-1 compound is a curcumin analog that possesses several curcumin characteristics, such as antiproliferative, antitumor and antimetastatic properties. The objective of this study was to evaluate the signaling pathways involved in melanoma cell death after treatment with DM-1 compared to the standard agent for melanoma treatment, DTIC. Altogether, these data confirm DM-1 as a chemotherapeutic agent with effective tumor control properties and a lower incidence of side effects in normal cells compared to DTIC.

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“…44 Single-agent chemotherapies, most commonly dacarbazine, have clinical activity in melanoma, but response rates for patients treated with such agents are low (ie, Ͻ25%). Response rates for patients treated with dacarbazine along with another class of chemotherapy agent are higher (ie, 14% to 37%); however, in randomized clinical trials, such combination chemotherapy regimens have not demonstrated superior results when compared with single-agent chemotherapy regimens.…”

Section: Discussionmentioning

confidence: 99%

Use of Gene Expression and Pathway Signatures to Characterize the Complexity of Human Melanoma

Freedman

Tyler

Nevins

et al. 2011

The American Journal of Pathology

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A defining characteristic of most human cancers is heterogeneity, resulting from the somatic acquisition of a complex array of genetic and genomic alterations. Dissecting this heterogeneity is critical to developing an understanding of the underlying mechanisms of disease and to paving the way toward personalized treatments of the disease. We used gene expression data sets from the analysis of primary and metastatic melanomas to develop a molecular description of the heterogeneity that characterizes this disease. Unsupervised hierarchical clustering, gene set enrichment analyses, and pathway activity analyses were used to describe the genetic heterogeneity of melanomas. Patterns of gene expression that revealed two distinct classes of primary melanoma, two distinct classes of in-transit melanoma, and at least three subgroups of metastatic melanoma were identified. Expression signatures developed to predict the status of oncogenic signaling pathways were used to explore the biological basis underlying these differential patterns of expression. This analysis of activities revealed unique pathways that distinguished the primary and metastatic subgroups of melanoma. Distinct patterns of gene expression across primary, in-transit, and metastatic melanomas underline the genetic heterogeneity of this disease. This heterogeneity can be described in terms of deregulation of signaling pathways, thus increasing the knowledge of the biological features underlying individual melanomas and potentially directing therapeutic opportunities to individual patients with melanoma.

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Chemotherapy and biologic therapies for melanoma: do they work?

Cited by 86 publications

References 99 publications

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

The curcumin analog DM-1 induces apoptotic cell death in melanoma

Use of Gene Expression and Pathway Signatures to Characterize the Complexity of Human Melanoma

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