S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas

Mehdi, Ali; Attias, Mikhaël; Arakelian, Ani; Szyf, Moshe; Piccirillo, Ciriaco A.; Rabbani, Shafaat A.

doi:10.1016/j.neo.2022.100874

Cited by 5 publications

(3 citation statements)

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“…1A and supplemental Fig S6). The data clearly show that B16F10, YUMM 1.7, and A375-MA1 cells had CD95 expression, which consistent with previous findings [28][29][30]. Radiation was applied on B16F10, YUMM 1.7, and A375-MA1 cells to determine the dose-dependency of cell death of cells upon radiation.…”

Section: Anti-cd95 Antibodies Boost Apoptosis After Radiationsupporting

confidence: 88%

The abscopal effect of anti-CD95 and radiotherapy in melanoma

et al. 2023

Discov Onc

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Background Radiotherapy (RT) is frequently adopted to control cancer cell proliferation, which is achieved by altering the tumor microenvironment (TME) and immunogenicity. Apoptosis of cancer cells is the major effect of radiation on tumor tissues. Fas/APO-1(CD95) receptors on the cell membrane are death receptors that can be activated by diverse factors, including radiation and integration with CD95L on CD8+ T cells. The abscopal effect is defined as tumor regression out of the local RT field, and it is produced through anti-tumor immunity. The immune response against the radiated tumor is characterized by the cross-presentation between antigen-presenting cells (APCs), which includes cytotoxic T cells (CTLs) and dendritic cells (DCs). Methods The effect of activation and radiation of CD95 receptors on melanoma cell lines was examined in vivo and in vitro. In vivo, bilateral lower limbs were given a subcutaneous injection of a dual-tumor. Tumors in the right limb were radiated with a single dose of 10 Gy (primary tumor), while tumors in the left limb (secondary tumor) were spared. Results The anti-CD95 treatment plus radiation (combination treatment) reduced growth rates of both primary and secondary tumors relative to the control or radiation groups. In addition, higher degrees of infiltrating CTLs and DCs were detected in the combination treatment compared to the other groups, but the immune response responsible for secondary tumor rejection was not proven to be tumor specific. In vitro, combination treatment combined with radiation resulted in further apoptosis of melanoma cells relative to controls or cells treated with radiation. Conclusions Targeting CD95 on cancer cells will induce tumor control and the abscopal effect.

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Section: Anti-cd95 Antibodies Boost Apoptosis After Radiationsupporting

confidence: 88%

The abscopal effect of anti-CD95 and radiotherapy in melanoma

et al. 2023

Discov Onc

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“…Under physiological conditions, exposure to UV radiation induces the release of α-MSH from keratinocytes that binds the MC1R on melanocytes membrane activating MITF through the cAMP-PKA-CREB axis. MITF, in turn, increases the expression of proliferation and survival signals (genes such as CDK2 and BCL-2 ) [ 47 ], melanin-related genes including TYR , TYRP1 , TYRP2 , and genes related to melanosome maturation as well as PMEL17 and MLANA (MART-1 or MELAN-A) [ 48 , 49 ]. MITF expression is also correlated to the invasive capacity of melanoma cells and regulates the transition between proliferative and invasive states (“phenotype switching”) [ 50 ].…”

Section: Biological Aspects Of Braf Mutationsmentioning

confidence: 99%

“…Since TYR, TYRP1, TYRP2, PMEL, and MELAN-A are recognised as melanocyte differentiation antigens (MDAs), inhibition of BRAF V600E increases MDAs expression, through the upregulation of MITF, enhancing melanoma immunogenicity [ 49 ]. In addition to the mechanisms previously described, there is further evidence of a link between BRAF mutational status and melanoma immunogenicity.…”

Section: Biological Aspects Of Braf Mutationsmentioning

confidence: 99%

BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers

Castellani

Buccarelli

Arasi

et al. 2023

Cancers

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Melanoma is an aggressive form of skin cancer resulting from the malignant transformation of melanocytes. Recent therapeutic approaches, including targeted therapy and immunotherapy, have improved the prognosis and outcome of melanoma patients. BRAF is one of the most frequently mutated oncogenes recognised in melanoma. The most frequent oncogenic BRAF mutations consist of a single point mutation at codon 600 (mostly V600E) that leads to constitutive activation of the BRAF/MEK/ERK (MAPK) signalling pathway. Therefore, mutated BRAF has become a useful target for molecular therapy and the use of BRAF kinase inhibitors has shown promising results. However, several resistance mechanisms invariably develop leading to therapeutic failure. The aim of this manuscript is to review the role of BRAF mutational status in the pathogenesis of melanoma and its impact on differentiation and inflammation. Moreover, this review focuses on the mechanisms responsible for resistance to targeted therapies in BRAF-mutated melanoma and provides an overview of circulating biomarkers including circulating tumour cells, circulating tumour DNA, and non-coding RNAs.

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