Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy

Abstract

Although most melanoma cases may be treated by surgical intervention upon early diagnosis, a significant portion of patients can still be refractory, presenting low survival rates within 5 years after the discovery of the illness. As a hallmark, melanomas are highly prone to evolve into metastatic sites. Moreover, melanoma tumors are highly resistant to most available drug therapies and their incidence have increased over the years, therefore leading to public health concerns about the development of novel therapies. Therefore, researches are getting deeper in unveiling the mechanisms by which melanoma initiation can be triggered and sustained. In this context, important progress has been achieved regarding the roles and the impact of cellular signaling pathways in melanoma. This knowledge has provided tools for the development of therapies based on the intervention of signal(s) promoted by these cascades. In this review, we summarize the importance of major signaling pathways (mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)-Akt, Wnt, nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), transforming growth factor β (TGF-β) and Notch) in skin homeostasis and melanoma progression. Available and developing melanoma therapies interfering with these signaling cascades are further discussed.

Suppression of tumor growth and metastasis by ethanol extract of <i>Angelica dahurica Radix</i> in murine melanoma B16F10 cells

“…To solve this problem, a lot of researches are getting identification of the mechanisms by which melanoma initiation can be triggered and sustained. Recently, there are well known that melanoma may trigger not only the activation of RAS/MEK singling pathway, but also other pathways such as phosphoinositide 3-kinase (PI3K)/Akt and Wnt signaling pathways (57,58). In present study, we found that exposure to EEAD led to decrease protein expression of Akt and β-catenin in B16F10 cells (Supplementary Figure S1, http://www.…”

NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer

“…Approximately 2–3 million skin cancers cases are diagnosed each year and their incidence has increased over the last decades [207]. Skin tumors can be classified as non-melanomas (derived from keratinized epithelial cells) or melanomas (derived from melanocytes) [190,191].…”

“…Skin tumors can be classified as non-melanomas (derived from keratinized epithelial cells) or melanomas (derived from melanocytes) [190,191]. Melanoma accounts for 2% of the cases, being the most aggressive type of skin cancer, accounting for almost 10000 deaths per year [207,208].…”

<p>Decreasing Microtubule Actin Cross-Linking Factor 1 Inhibits Melanoma Metastasis by Decreasing Epithelial to Mesenchymal Transition</p>

“…Both the outgrowth of primary and metastatic melanoma pose significant and unprecedented clinical challenges. 1,2 Although surgical ablation is the most efficient treatment prior to melanoma invasion and the formation of metastases, a significant percentage of patients remains refractory. As a result, the five-year survival of patients is low, and malignant melanoma will become a formidable disease once cancer cells colonize other tissues.…”