Stemming the Rising Incidence of Melanoma: Calling Prevention to Action

Gershenwald, Jeffrey E.; Guy, Gery P.

doi:10.1093/jnci/djv381

Cited by 69 publications

(48 citation statements)

References 34 publications

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“…Melanoma is the deadliest form of skin cancer and one of the most rapidly growing cancers worldwide (9). The BRAF inhibitors (BRAFi) vemurafenib and dabrafenib or the MEK inhibitors trametinib and cobimetinib achieve remarkable antitumor responses in patients with BRAF V600E melanoma with improvements in overall survival.…”

Section: Introductionmentioning

confidence: 99%

Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas

Garandeau

Noujarède

Leclerc

et al. 2019

Molecular Cancer Therapeutics

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BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAF V600Emutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that is, a tendency for increased very long-chain ceramide species, in the plasma of patients with melanoma who achieve a response to BRAFi therapy as compared with patients with progressive disease. Treatment with BRAFi resulted in a strong decrease in S1PR1/3 expression in sensitive but not in resistant cells. Genetic and pharmacologic interventions, that increase ceramide/S1P ratio, downregulated S1PR expression and blocked BRAFi-resistant melanoma cell growth. This effect was associated with a decreased expression of MITF and Bcl-2. Moreover, the BH3 mimetic ABT-737 improved the antitumor activity of approaches targeting S1P-metabolizing enzymes in BRAFiresistant melanoma cells. Collectively, our findings indicate that targeting the S1P/S1PR axis could provide effective therapeutic options for patients with melanoma who relapse after BRAFi therapy.

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Section: Introductionmentioning

confidence: 99%

Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas

Garandeau

Noujarède

Leclerc

et al. 2019

Molecular Cancer Therapeutics

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“…The time is now for diverse disciplines in multiple sectors—health care, government, education, business, advocacy, and community—to coordinate efforts and leverage existing knowledge to make major strides in reducing the public health burden of melanoma in the United States. Examples of how clinicians and researchers are collaborating to embrace approaches with broad reach and maximal impact include The University of Texas MD Anderson Cancer Center's Melanoma Moon Shot, which, as a component of this broad effort, emphasizes a program of innovative behavioral research and dissemination of evidence‐based prevention strategies and public policy initiatives alongside a research focus on personalized melanoma treatment strategies (http://cancermoonshots.org/cancer-types/melanoma), and Oregon Health and Science University's War on Melanoma, which prioritizes research, public education, and early detection (http://www.ohsu.edu/xd/health/services/dermatology/war-on-melanoma/).…”

Section: Introductionmentioning

confidence: 99%

State of the science on prevention and screening to reduce melanoma incidence and mortality: The time is now

Tripp

Watson

Balk

et al. 2016

CA A Cancer J Clinicians

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159

141

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Although overall cancer incidence rates are decreasing, melanoma incidence rates continue to increase about 3% annually. Melanoma is a significant public health problem that exacts a substantial financial burden. Years of potential life lost from melanoma deaths contribute to the social, economic and human toll of this disease. However, most cases are potentially preventable. Research has clearly established that exposure to ultraviolet (UV) radiation increases melanoma risk. Unprecedented anti-tumor activity and evolving survival benefit from novel targeted therapies and immunotherapies are now available for patients with unresectable and/or metastatic melanoma. Still, prevention (minimizing sun exposure that may result in tanned or sunburned skin and avoiding indoor tanning) and early detection (identifying lesions before they become invasive, or at an earlier stage) have significant potential to reduce melanoma incidence and melanoma-associated deaths. This paper reviews the state of the science on prevention and early detection of melanoma, and current areas of scientific uncertainty and ongoing debate. The US Surgeon General’s Call to Action to Prevent Skin Cancer and US Preventive Services Task Force reviews on skin cancer have propelled a national discussion on melanoma prevention and screening that makes this an extraordinary and exciting time for diverse disciplines in multiple sectors – health care, government, education, business, advocacy and community – to coordinate efforts and leverage existing knowledge to make major strides in reducing the public health burden of melanoma in the US.

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“…Therefore, identifying suitable molecular target drugs to inhibit MM-associated pathways is likely to improve the survival rates and prognosis of patients with MM (18). As one of the most important proangiogenic factors, VEGF is expressed in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Gefitinib inhibits malignant melanoma cells through the VEGF/AKT signaling pathway

et al. 2018

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Malignant melanoma (MM) is caused by melanophore cancerization in tissue pigmentation regions, leading to skin, mucous membrane, eye and central nervous system carcinogenesis. The incidence of MM has increased in previous years, and it has become the primary cause of skin cancer‑associated mortality in developed countries. MM is characterized as highly malignant and readily metastasized, and has a poor prognosis. Targeting angiogenesis is an important method for MM treatment. As an important proangiogenic factor in tumor growth and metastasis, vascular endothelial growth factor (VEGF) can promote neovascularization and increase vascular permeability. Gefitinib is a novel drug targeting VEGF. The effect and mechanism of gefitinib on MM remain to be elucidated, and were investigated in the present study. The A375 MM cell line was used in the present study; it was cultured in vitro and divided into gefitinib groups (5 and 10 µM) and a control group. Cell proliferation was measured using an MTT assay and the activity of caspase‑3 was assessed using a kit. Cell invasive ability was determined using a Transwell chamber. The mRNA and protein expression levels of VEGF and AKT were detected using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Gefitinib significantly inhibited MM cell proliferation, enhanced the activity of caspase 3 and suppressed tumor cell invasion (P<0.05). In addition, gefitinib significantly downregulated the mRNA and protein expression levels of VEGF and AKT, and these changes were dose‑dependent (P<0.05). Taken together, gefitinib suppressed MM cell proliferation and invasion in vitro by regulating the VEGF/AKT signaling pathway.

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Stemming the Rising Incidence of Melanoma: Calling Prevention to Action

Cited by 69 publications

References 34 publications

Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas

Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas

State of the science on prevention and screening to reduce melanoma incidence and mortality: The time is now

Gefitinib inhibits malignant melanoma cells through the VEGF/AKT signaling pathway

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