Non-melanoma skin cancer pathogenesis

MDC1 (Mediator of DNA damage Checkpoint protein 1) functions to facilitate the localization of numerous DNA damage response (DDR) components to DNA double-strand break sites. MDC1 is an integral component in preserving genomic stability and appropriate DDR regulation. There haven't been systematic investigations of MDC1 mutations that induce cancer and genomic instability. Variations in nsSNPs have the potential to modify the protein chemistry and their function. Describing functional SNPs in disease-associated genes presents a significant conundrum for investigators, it is possible to assess potential functional SNPs before conducting larger population examinations...

To assess the possible beneficial effects of drugs and drug candidates, different dermatological disease models are available in rodents. These models are able to mimic one or more characteristic features of the disorders, but not completely recapitulate the pathogenesis of the human skin diseases. Therefore, to improve the technology many new models have been developed both by genetic engineering and by chemical or physical induction. Currently the in vivo rodent models provide the physiologically most relevant approach to produce the pathology related to the majority of dermatological diseases...

Background and Objectives : Previous studies revealed the anti-angiogenic, antiproliferative, and anti-inflammatory effects of Vitamin D (VitD) on cancer cells. Although this body of evidence supported the correlation of high VitD levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). The aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on VitD serum status, dietary intake, and VitD receptor (VDR) polymorphisms in correlation to NMSC incidence...

Human papillomaviruses (HPVs) represent a diverse group of DNA viruses that infect epithelial cells of mucosal and cutaneous tissues, leading to a wide spectrum of clinical outcomes. Among various HPVs, alpha (α) and beta (β) types have garnered significant attention due to their associations with human health. α-HPVs are primarily linked to infections of the mucosa, with high-risk subtypes, such as HPV16 and HPV18, being the major etiological agents of cervical and oropharyngeal cancers. In contrast, β-HPVs are predominantly associated with cutaneous infections and are commonly found on healthy skin...

PURPOSE OF REVIEW: This review focuses on updates in prognosis, pathogenesis, and treatment of cutaneous T cell lymphoma (CTCL). RECENT FINDINGS: Cohort studies indicate imaging may be necessary in early-stage CTCL. Risk factors for progression of CTCL have been identified. Interactions between malignant cells and the tumor microenvironment (TME) and the skin microbiome advance the understanding of pathogenesis and tumor cell dissemination. Studies support a hypothesis of circulating malignant tumor cells...

Malignant melanoma (MM) is the most common and deadliest type of skin cancer and is associated with high mortality rates across all races and ethnicities. Although present treatment options combined with surgery provide short-term clinical benefit in patients and early diagnosis of non-metastatic MM significantly increases the probability of survival, no efficacious treatments are available for MM. The etiology and pathogenesis of MM are complex. Acquired drug resistance is associated with a pool prognosis in patients with advanced-stage MM...

Melanoma is a rare but highly lethal type of skin cancer whose incidence is increasing globally. Melanoma is characterized by high resistance to therapy and relapse. Despite significant advances in the treatment of metastatic melanoma, many patients experience progression due to resistance mechanisms. Epigenetic changes, including alterations in chromatin remodeling, DNA methylation, histone modifications, and non-coding RNA rearrangements, contribute to neoplastic transformation, metastasis, and drug resistance in melanoma...

Morbidity and mortality from skin cancer continue to rise domestically and globally, and melanoma and non-melanoma skin cancers are a topic of interest in the dermatology and oncology communities. In this review, we summarize the stimulator of interferon genes (STING) pathway, its specific role in the pathogenesis of DNA damage and skin cancer, and STING-specific therapies that may fight both melanoma and non-melanoma skin (NMSC) cancers. Furthermore, we discuss specific portions of the STING pathway that may be used in addition to previously used therapies to provide a synergistic effect in future oncology treatments and discuss the limitations of current STING-based therapies...

Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the current review with an eye toward potential therapeutic treatments. LncRNAs are remarkably adaptable, acting as scaffolding, guides, or decoys to modify key signaling pathways (i.e., the Wnt/β-catenin pathway) and gene expression...

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...

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma. Despite the recent cascade of molecular investigations, no universal molecular signature has been identified as responsible for MCC's pathogenesis. The microRNAs (miRNAs) play a critical role in the post-transcriptional regulation of gene expression...

The development of immune checkpoint inhibitors (ICIs) has dramatically altered the landscape of therapy for multiple malignancies, including urothelial carcinoma, non-small cell lung cancer, melanoma and gastric cancer. As part of their anti-tumor properties, ICIs can enhance susceptibility to inflammatory side effects known as immune-related adverse events (irAEs), in which the skin is one of the most commonly and rapidly affected organs. Although numerous questions still remain unanswered, multi-omics technologies have shed light into immunological mechanisms, as well as the correlation between ICI-induced activation of immune systems and the incidence of cirAE (cutaneous irAEs)...

The incidence of non-melanoma skin cancer (NMSC) continues to rise, and more than one million cases are diagnosed in the United States each year. The increase in prevalence has been attributed to increased lifespan and improvements in survival for conditions that increase the risk of these malignancies. Patients who are immunocompromised have a higher risk of developing NMSC compared to the general population. In immunosuppressed patients, a combination of prevention, frequent surveillance, and early intervention are necessary to reduce morbidity and mortality...

Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have demonstrated that patients suffering from mastocytosis face an increased risk of melanoma and non-melanoma skin cancer. The cause of this has not yet been clearly identified. In the literature, the potential influence of several factors has been suggested, including genetic background, the role of cytokines produced by mast cells, iatrogenic and hormonal factors...

Ultraviolet (UV) radiation is a strong environmental carcinogen responsible for the pathogenesis of most skin cancers, including malignant melanoma (MM) and non-melanoma (keratinocyte) skin cancers. The carcinogenic role of UV was firmly established based on epidemiological evidence and molecular findings of the characteristic mutation signatures which occur during the excision repair of cyclobutane pyrimidine dimers and 6,4-photoproducts. The role of UV in the pathogenesis of mycosis fungoides (MF), the most common type of primary cutaneous T-cell lymphoma, remains controversial...

BACKGROUND/AIM: Cutaneous squamous cell carcinoma (cSCC) is a common non-melanoma skin cancer, and its incidence is increasing. Proteasome subunit alpha type-7 (PSMA7) has been found to be aberrantly expressed in several cancers. However, whether it functions as a tumor suppressor or oncogene in the pathogenesis of cancers, particularly cSCC, remains controversial. Here, we aimed to investigate the functions of PSMA7 in cSCC pathogenesis. PATIENTS AND METHODS: Clinicopathological characteristics were evaluated in 131 patients with cSCC using tissue sections...

Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of β-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective β-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together...

BACKGROUND: Melanoma represents the deadliest skin cancer due to its cell plasticity which results in high metastatic potential and chemoresistance. Melanomas frequently develop resistance to targeted therapy; therefore, new combination therapy strategies are required. Non-canonical signaling interactions between HH-GLI and RAS/RAF/ERK signaling were identified as one of the drivers of melanoma pathogenesis. Therefore, we decided to investigate the importance of these non-canonical interactions in chemoresistance, and examine the potential for HH-GLI and RAS/RAF/ERK combined therapy...

The pathogenesis of keratinocytic skin cancer has been well-studied over the years, with a main focus on the influence of UV radiation and the subsequent changes in the genome regulator p53, which affects the cell cycle and the programmed cell death, apoptosis. Alarming and relatively new trend is the link between nitrosamines in blood pressure medications (but not only) and the development of both melanocytic and keratinocytic skin tumors. In the recent past, high concentrations (above the so-called daily acceptable intake dose) of nitrosamines in ACE inhibitors and sartans became the reason for some of these medications to be officially withdrawn from the drug market...

BACKGROUND: The Skin Investigation Network of Canada (SkIN Canada) is a new national skin research network. To shape the research landscape and ensure its value to patient care, research priorities that are important to patients, caregivers, and health care providers must be identified. OBJECTIVES: To identify the Top Ten research priorities for 9 key skin conditions. METHODS: We first surveyed health care providers and researchers to select the top skin conditions for future research within the categories of inflammatory skin disease, skin cancers (other than melanoma), and wound healing...