The Dynamics of ERK Signaling in Melanoma, and the Response to BRAF or MEK Inhibition, Are Cell Cycle Dependent

Simpson, Chloe; Bakal, Chris

doi:10.2139/ssrn.3188455

Cited by 2 publications

(2 citation statements)

References 84 publications

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“…Furthermore, ERK activation might also be involved in chemoresistance. Taken together, these data suggest that the inhibition of ERK is a potential therapeutic approach for melanoma treatment [58,59]. Another mechanism that can be potentially targeted for therapeutic purposes is the so-called Epithelial to Mesenchymal Transition (EMT) that involves changes in marker expression, which can be correlated to melanoma's invasiveness and progression as well as to survival outcomes.…”

Section: Mutational Burdenmentioning

confidence: 97%

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

et al. 2021

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Cutaneous melanoma is one of the most aggressive solid tumors, with a low survival for the metastatic stage. Currently, clinical melanoma treatments include surgery, chemotherapy, targeted therapy, immunotherapy and radiotherapy. Of note, innovative therapeutic regimens concern the administration of multitarget drugs in tandem, in order to improve therapeutic efficacy. However, also, if this drug combination is clinically relevant, the patient’s response is not yet optimal. In this scenario, nanotechnology-based delivery systems can play a crucial role in the clinical treatment of advanced melanoma. In fact, their nano-features enable targeted drug delivery at a cellular level by overcoming biological barriers. Various nanomedicines have been proposed for the treatment of cutaneous melanoma, and a relevant number of them are undergoing clinical trials. In Italy, researchers are focusing on the pharmaceutical development of nanoformulations for malignant melanoma therapy. The present review reports an overview of the main melanoma-addressed nanomedicines currently under study in Italy, alongside the state of the art of melanoma therapy. Moreover, the latest Italian advances concerning the pre-clinical evaluation of nanomedicines for melanoma are described.

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Section: Mutational Burdenmentioning

confidence: 97%

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

et al. 2021

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“…In addition to its anti-migratory and anti-metastatic properties, CCG-203971 induced G1-cell cycle arrest in melanoma cells. The recent observation that melanoma cells arrested in the G1 phase have higher sensitivity to MEK inhibitors (29), suggests a potential benefit of combination treatment with MEK inhibitors and Rho/MRTF pathway inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines

Appleton

Palsuledesai

Misek

et al. 2019

Preprint

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The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (~50% BRAF V600 mutations and ~30% NRAS mutations). While targeted therapies have yielded success in BRAF V600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in SK-Mel-147 cells which have a high level of trametinib resistance. These findings suggest a role of the Rho/MRTF-pathway in intrinsic trametinib resistance in a subset of NRAS mutant melanoma cell lines and highlights the potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.

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The Dynamics of ERK Signaling in Melanoma, and the Response to BRAF or MEK Inhibition, Are Cell Cycle Dependent

Cited by 2 publications

References 84 publications

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines

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