Targeted Therapies for Melanoma

Smetana, Karel; Lacina, Lukáš; Kodet, Ondřej

doi:10.3390/cancers12092494

Cited by 9 publications

(10 citation statements)

References 15 publications

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“…Intracellular signaling through KIT plays a critical role in melanocyte development. For the last ten years, it has had an emerging role as an oncogene and therapeutic target in melanoma 62–64 . KIT mutations are found in only 3% of all melanomas but a disproportionate amount of KIT aberrations has been identified in melanoma arising from chronically sun‐damaged skin in acral and mucosal tissue; the N566D mutation being among the most commonly found in this gene 65,66 .…”

Section: Resultsmentioning

confidence: 99%

“…For the last ten years, it has had an emerging role as an oncogene and therapeutic target in melanoma. [62][63][64] KIT mutations are found in only 3% of all melanomas but a disproportionate amount of KIT aberrations has been identified in melanoma arising from chronically sun-damaged skin in acral and mucosal tissue; the N566D mutation being among the most commonly found in this gene. 65,66 KIT mutations are nearly always mutually exclusive with NRAS or BRAF and thus define a unique subtype of melanoma.…”

Section: Identification Of Melanoma Protein Mutationsmentioning

confidence: 99%

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The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

Betancourt

Gil

Sánchez

et al. 2021

Clinical & Translational Med

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Section: Resultsmentioning

confidence: 99%

Section: Identification Of Melanoma Protein Mutationsmentioning

confidence: 99%

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

Betancourt

Gil

Sánchez

et al. 2021

Clinical & Translational Med

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“…Despite remarkable progress in CMM-targeted therapy and immunotherapy, the metastatic disease represents a therapeutic challenge and leaves patients with an uncertain prognosis (Smetana et al 2020 ). From this perspective, identification of new therapeutic targets is critical to manage CMM successfully (Brustugun et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts

Strnadová

Pfeiferová

Přikryl

et al. 2021

Histochem Cell Biol

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The incidence of cutaneous malignant melanoma is increasing worldwide. While the treatment of initial stages of the disease is simple, the advanced disease frequently remains fatal despite novel therapeutic options . This requires identification of novel therapeutic targets in melanoma. Similarly to other types of tumours, the cancer microenvironment plays a prominent role and determines the biological properties of melanoma. Importantly, melanoma cell-produced exosomes represent an important tool of intercellular communication within this cancer ecosystem. We have focused on potential differences in the activity of exosomes produced by melanoma cells towards melanoma-associated fibroblasts and normal dermal fibroblasts. Cancer-associated fibroblasts were activated by the melanoma cell-produced exosomes significantly more than their normal counterparts, as assessed by increased transcription of genes for inflammation-supporting cytokines and chemokines, namely IL-6 or IL-8. We have observed that the response is dependent on the duration of the stimulus via exosomes and also on the quantity of exosomes. Our study demonstrates that melanoma-produced exosomes significantly stimulate the tumour-promoting proinflammatory activity of cancer-associated fibroblasts. This may represent a potential new target of oncologic therapy .

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“…Additionally, previous X-ray crystallographic studies have shown that imatinib can bind to the inactive conformation of c-KIT, further validating this hypothesis [ 151 ]. FGF2 is a growth factor shown to induce resistance to nilotinib, a second-generation drug of the imatinib family, likely through activation of the MAPK pathway [ 158 , 159 ]. Ponatinib is a multi-target TKI previously approved to treat chronic myeloid leukemia (CML) caused by BCR-ABL fusion.…”

Section: C-kitmentioning

confidence: 99%

Resistance to Molecularly Targeted Therapies in Melanoma

Patel

Eckburg

Gantiwala

et al. 2021

Cancers

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Malignant melanoma is the most aggressive type of skin cancer with invasive growth patterns. In 2021, 106,110 patients are projected to be diagnosed with melanoma, out of which 7180 are expected to die. Traditional methods like surgery, radiation therapy, and chemotherapy are not effective in the treatment of metastatic and advanced melanoma. Recent approaches to treat melanoma have focused on biomarkers that play significant roles in cell growth, proliferation, migration, and survival. Several FDA-approved molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) have been developed against genetic biomarkers whose overexpression is implicated in tumorigenesis. The use of targeted therapies as an alternative or supplement to immunotherapy has revolutionized the management of metastatic melanoma. Although this treatment strategy is more efficacious and less toxic in comparison to traditional therapies, targeted therapies are less effective after prolonged treatment due to acquired resistance caused by mutations and activation of alternative mechanisms in melanoma tumors. Recent studies focus on understanding the mechanisms of acquired resistance to these current therapies. Further research is needed for the development of better approaches to improve prognosis in melanoma patients. In this article, various melanoma biomarkers including BRAF, MEK, RAS, c-KIT, VEGFR, c-MET and PI3K are described, and their potential mechanisms for drug resistance are discussed.

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Targeted Therapies for Melanoma

Abstract: The incidence of cutaneous malignant melanoma (CMM) is significantly increasing worldwide.[...]

Cited by 9 publications

References 15 publications

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts

Resistance to Molecularly Targeted Therapies in Melanoma

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