Pevonedistat targeted therapy inhibits canine melanoma cell growth through induction of DNA re‐replication and senescence

Wood, Elizabeth; Lu, Zhenzhen; Jia, Shuai; Assumpção, Anna L F. V.; Hesteren, Matthew A. Van; Huelsmeyer, M. K.; Vail, David M.; Pan, Xuan

doi:10.1111/vco.12546

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…Pevonedistat (MLN4924) leads to DNA re-replication, cell cycle arrest and death via targeting the NEDD8-activating enzyme (NAE). It has anti-tumor activity and supports the clinical benefits observed in recent clinical trials in SKCM patients ( Wong et al, 2017 ; Wood et al, 2020 ). For immunotherapy, the combination of pevonedistat and anti-PD-L1therapy had a better therapeutic efficacy compared to each agent alone.…”

Section: Discussionsupporting

confidence: 77%

A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma

Huang

et al. 2023

Front. Genet.

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Background: Ferroptosis is an iron-dependent cell death mode and closely linked to various cancers, including skin cutaneous melanoma (SKCM). Although attempts have been made to construct ferroptosis-related gene (FRG) signatures for predicting the prognosis of SKCM, the prognostic impact of ferroptosis-related genetic mutations in SKCM remains lacking. This study aims to develop a prediction model to explain the relationship between ferroptosis-related genetic mutations and clinical outcomes of SKCM patients and to explore the potential value of ferroptosis in SKCM treatment.Methods: FRGs which significantly correlated with the prognosis of SKCM were firstly screened based on their single-nucleotide variant (SNV) status by univariate Cox regression analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) and Cox regressions were performed to construct a new ferroptosis-related genetic mutation risk (FerrGR) model for predicting the prognosis of SKCM. We then illustrate the survival and receiver operating characteristic (ROC) curves to evaluate the predictive power of the FerrGR model. Moreover, independent prognostic factors, genomic and clinical characteristics, immunotherapy, immune infiltration, and sensitive drugs were compared between high—and low—FerrGR groups.Results: The FerrGR model was developed with a good performance on survival and ROC analysis. It was a robust independent prognostic indicator and followed a nomogram constructed to predict prognostic outcomes for SKCM patients. Besides, FerrGR combined with tumor mutational burden (TMB) or MSI (microsatellite instability) was considered as a combined biomarker for immunotherapy response. The high FerrGR group patients were associated with an inhibitory immune microenvironment. Furthermore, potential drugs target to high FerrGR samples were predicted.Conclusion: The FerrGR model is valuable to predict prognosis and immunotherapy in SKCM patients. It offers a novel therapeutic option for SKCM.

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Section: Discussionsupporting

confidence: 77%

A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma

Huang

et al. 2023

Front. Genet.

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“…However, when the isolation was effective, no morphological differences were observed between the melanocytes obtained with the two methods. Scientific reports on the isolation and cultivation of both canine and human neoplastic melanocytes, regardless of the technique used (spontaneous migration or enzymatic digestion), frequently favor a flask incubation of the cells, although occasionally plate seeding is described [ 1 , 11 , 12 , 19 , 31 ] . Accordingly, we preferred the enzymatic digestion as a larger number of cells was obtained in less time.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Primary Cultures of Normal and Neoplastic Canine Melanocytes

Sforna

Chiaradia

Porcellato

et al. 2021

Animals

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Although numerous animal models, especially mouse models, have been established for the study of melanoma, they often fail to accurately describe the mechanisms of human disease because of their anatomic, physiological, and immune differences. The dog, as a spontaneous model of melanoma, is nowadays considered one of the most valid alternatives due to the heterogeneity of clinical presentations and of histological and genetic similarities of canine melanoma with the human counterpart. The aim of the study was to optimize a protocol for the isolation and cultivation of healthy and neoplastic canine melanocytes derived from the same animal and obtained from cutaneous and mucosal (oral) sites. We obtained five primary tumor cell cultures (from 2 cutaneous melanoma, 2 mucosal melanoma and 1 lymph node metastasis) and primary normal melanocyte cell cultures (from normal skin and mucosa) from the same dogs. Immunocytochemical characterization with Melan A, PNL2 and S100 antibodies confirmed the melanocytic origin of the cells. This work contributes to expanding the case record of studies on canine melanoma cell cultures as suitable model to study human and canine melanoma. To the authors’ knowledge, this is the first report of isolation of normal skin and mucosal canine melanocytes.

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“…These results showed that CRL4-CDT2-SET8/p21 degradation axis could be the main target of MLN4924 in melanoma 103 . Similarly, Wood and co-workers discovered that MLN4924 dramatically inhibited the viability of canine melanoma cells, and induced apoptosis by induction of DNA re-replication and cell senescence 104 . Moreover, most canine melanoma samples displayed sensitivity to MLN4924 of nanomolar concentration, which was related to P21 levels.…”

Section: Neddylation In Cancersmentioning

confidence: 93%

Targeting cullin neddylation for cancer and fibrotic diseases

He,

Yang,

Zengyangzong

et al. 2023

Theranostics

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Protein neddylation is a post-translational modification, and its best recognized substrates are cullin family proteins, which are the core component of Cullin-RING ligases (CRLs). Given that most neddylation pathway proteins are overactivated in different cancers and fibrotic diseases, targeting neddylation becomes an emerging approach for the treatment of these diseases. To date, numerous neddylation inhibitors have been developed, of which MLN4924 has entered phase I/II/III clinical trials for cancer treatment, such as acute myeloid leukemia, melanoma, lymphoma and solid tumors. Here, we systematically describe the structures and biological functions of the critical enzymes in neddylation, highlight the medicinal chemistry advances in the development of neddylation inhibitors and propose the perspectives concerning targeting neddylation for cancer and fibrotic diseases.

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Pevonedistat targeted therapy inhibits canine melanoma cell growth through induction of DNA re‐replication and senescence

Cited by 5 publications

References 36 publications

A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma

A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma

Characterization of Primary Cultures of Normal and Neoplastic Canine Melanocytes

Targeting cullin neddylation for cancer and fibrotic diseases

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