Search Results (534)

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Non-melanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), represents the most common type of cancer worldwide, particularly among Caucasians. While BCC is locally invasive with minimal metastatic potential, cSCC is a highly aggressive tumor with a significant potential for metastasis, particularly in elderly populations. Tumor development and progression and the metastasis of cSCC are influenced by a complex interplay between tumor cells and the tumor microenvironment. Recent research highlights the importance of various immune cell subsets, including T cells, tumor-associated macrophages (TAMs), and dendritic cells, in influencing tumor progression, immune evasion, and treatment resistance. This review outlines key regulatory mechanisms in the immune tumor microenvironment (TME) of cSCC and explores the role of cytokines, immune checkpoints, and stromal interactions. We further discuss the relevance of three-dimensional (3D) in vitro models such as spheroids, organoids, and tumor-on-chip systems as tools to mimic immune–tumor interactions with higher physiological relevance, such as macrophage activation and polarization against cSCC cells. Globally, 3D models offer new opportunities for immunotherapy screening and mechanistic studies. Understanding the immune landscape in cSCC through advanced modeling techniques holds strong clinical potential for improving diagnostic and therapeutic strategies. Full article

Malignant cutaneous melanoma is among the most aggressive forms of skin cancer, characterized by high metastatic potential and frequent resistance to standard therapies. Hydroxytyrosol, a phenolic compound derived from extra virgin olive oil, has shown promising anticancer properties in various models, yet its effects in 3D melanoma systems remain poorly understood. In this study, we used paired 3D spheroid models of non-tumorigenic (HEMa) and melanoma (C32) to assess the therapeutic potential of hydroxytyrosol. To evaluate the anti-tumoral effect of hydroxytyrosol, we performed cytotoxicity, metastasis, invasiveness, cell cycle arrest, apoptotic, and proteomic assays. Hydroxytyrosol treatment significantly impaired spheroid growth, reduced cell viability, and induced cell cycle arrest and apoptosis in C32 spheroids, with minimal cytotoxicity observed in HEMa models. Proteomic profiling further demonstrated that hydroxytyrosol selectively downregulated a network of oncogenic proteins, including ERBB2, ERBB3, ERBB4, VEGFR-2, and WIF-1, along with suppression of downstream PI3K-Akt and MAPK/ERK signaling pathways. In conclusion, compared to dabrafenib, hydroxytyrosol exerted a broader range of molecular effects and was more selective toward tumor cells. These findings support the use of hydroxytyrosol as a multi-targeted agent capable of attenuating melanoma progression through suppression of kinase signaling and tumor-stromal interactions. Full article

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article

Background/Objectives: The gold standard of treatment for both melanoma and non-melanoma skin cancers is wide surgical resection to obtain oncological radicality, which occasionally results in functional or aesthetic impairment, potentially affecting quality of life. Despite the increased complexity of the technique, extended duration of hospitalization, and prolonged surgical operative times, microsurgery can facilitate the reconstruction of locally invasive skin cancers following ablative surgery and may yield superior functional and aesthetic outcomes. Consequently, microsurgical reconstruction is more likely to be necessary if a large skin tumor requires excision. However, the impact of this extensive and complex procedure on patients with skin cancer has not yet been fully elucidated. The objective of this research was to critically analyze the utilization of free flap reconstruction subsequent to skin cancer therapy. Through a comprehensive examination of published data, this study aimed to assess the potential benefits and drawbacks associated with this reconstructive approach. Methods: A systematic review of studies that were published from January 2004 to May 2024 was conducted using the MEDLINE online database search. To present an evidence summary and provide a systematic approach and quality assessment, the GRADE^® rating was applied to the results. Results: This review summarizes the oncological and clinical data, including previous interventions, adjuvant and neoadjuvant therapies, nodal status, distant metastasis, and follow-up time. Surgical outcome parameters such as healing time, flap survival, revision rate success, and minor and major complications were documented. Along with the findings, a quality assessment of the studies was also provided. Conclusions: This systematic review underscores the extensive use and efficacy of microsurgery for reconstruction after skin cancer excision; however, the literature remains limited by inconsistent reporting of oncological outcomes and the lack of a standardized approach to evaluate the impact of free flap reconstruction on both immediate and long-term cancer-specific results. Full article

This narrative review examines the efficacy, cost-effectiveness, and aesthetic outcomes of Mohs micrographic surgery (MMS) compared to standard excision for treating non-melanoma skin cancers (NMSCs). A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Cochrane Library, covering studies published from 2000 to 2024. Key terms such as “Mohs Micrographic Surgery,” “non-melanoma skin cancer,” “recurrence rates,” “cost-effectiveness,” and “aesthetic outcomes” were utilized. Inclusion criteria encompassed peer-reviewed articles, clinical trials, and observational studies focusing on MMS and standard excision outcomes. Exclusion criteria included studies with inadequate data or those not published in English. The review highlights the superior oncologic outcomes of MMS, its cost-effectiveness over the long term, and comparable aesthetic results to standard excision principally. Methods: This narrative review was conducted following established guidelines for reporting narrative reviews. A systematic search strategy was employed across selected databases, with the last search conducted in May 2025. The search terms used were “Mohs Micrographic Surgery,” “non-melanoma skin cancer,” “recurrence rates,” “cost-effectiveness,” and “aesthetic outcomes.” Studies included were published between 2000 and 2024, in English, and provided data on the specified outcomes. Results: The majority of studies indicated that MMS offers superior recurrence-free survival rates compared to standard excision. Regarding cost-effectiveness, MMS was found to be more economical over the long term due to reduced recurrence rates and the need for fewer re-excisions. Aesthetic outcomes were comparable between MMS and standard excision, with both methods yielding satisfactory results. Discussion: The findings of this review support the use of MMS as a preferred treatment for high-risk NMSCs, particularly in cosmetically sensitive areas. While MMS may involve higher initial costs, its long-term cost-effectiveness and superior oncologic outcomes justify its use. The aesthetic outcomes associated with MMS are comparable to those of standard excision, making it a viable option for patients concerned with cosmetic results. Limitations: This review acknowledges several limitations, including the heterogeneity of study designs and potential selection biases inherent in the included studies. Additionally, the absence of randomized controlled trials comparing MMS and standard excision directly limits the strength of the conclusions drawn. Conclusions: This narrative review underscores the advantages of MMS in treating high-risk NMSCs, particularly in terms of recurrence rates and long-term cost-effectiveness. While both MMS and standard excision offer comparable aesthetic outcomes, the superior oncologic results of MMS make it a preferable option in certain clinical scenarios. Full article

Skin cancer, including melanoma and non-melanoma cancers (basal and squamous cell carcinomas), is the most common type of cancer. UV radiation, family history, and genetic predisposition are the main risk factors. Although surgical excision is the standard treatment, essential oils are attracting growing interest for their anti-cancer effects. This study tested the effects of Juniperus excelsa M. Bieb. (Cupressaceae), Lavandula vera DC. (Lamiaceae), and Salvia fruticosa (Mill). (Lamiaceae) essential oils extracted from Middle Eastern medicinal plants on HaCaT (normal), A5 (benign), and II4 (low-grade malignant) keratinocytes. Essential oils were extracted from Juniperus excelsa, Lavandula vera, and Salvia libanotica using steam distillation and then were chemically analyzed. The oils were sterilized, dissolved in DMSO, and prepared at concentrations of 0.75, 0.5, and 0.25 mg/mL. Human keratinocyte (HaCaT), benign (A5), and malignant (II4) cell lines were cultured in DMEM and treated with the essential oils for 24 or 48 h. Cell viability was assessed using the Trypan Blue Exclusion Test, while cell proliferation was evaluated using the MTT assay. Statistical analysis was performed using ANOVA with appropriate post hoc tests, considering p < 0.05 as significant. The results show that J. excelsa is cytotoxic but lacks selectivity, limiting its efficacy. In contrast, L. vera and S. fruticosa preferentially target malignant cells, particularly at low concentrations, while sparing normal cells. These oils have dose-dependent anticancer effects, with L. vera efficacy increasing as the concentration increases. In conclusion, L. vera and S. fruticosa are promising candidates for the treatment of skin cancer, although further in vivo studies are required. Full article

Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as ≥9 BCCs within 3 years. Objective: To analyse demographic, clinical, and histopathological features of non-syndromic HF-BCC in a Belgian cohort, compared with low-burden BCC patients and healthy controls. Methods: A retrospective cohort study was conducted at Erasme Hospital (Brussels) using data from the EUSCAP platform. Clinical, behavioural, and histopathological data were collected and statistically analysed. Results: Of 783 patients, 16 with HF-BCC were identified. For comparison, 32 patients with 1–2 BCCs and 117 patients without BCC were selected. HF-BCC patients showed distinct characteristics, including a higher proportion of superficial BCCs (68.3% vs. 50%, p = 0.01) and fewer nodular subtypes (43.2% vs. 63.5%, p = 0.01). Their tumours were less frequently located on the nose and ears compared with patients having 1–2 BCCs. HF-BCC was associated with a personal history of squamous cell carcinoma (SCC) and actinic keratosis (AK). Conclusions: HF-BCC patients display distinct anatomical, histopathological and clinical characteristics, with a predominance of superficial BCC and an association with a personal history of SCC and AK. They show a lower frequency of tumours on the nose and ears, with a stronger tendency for localisation on the trunk and extremities. Identifying risk factors and genetic markers may contribute to improved early detection strategies, preventive measures, and the development of targeted therapies. Full article

Background/Objectives: Non-melanoma skin cancer (NMSC) is among the most common cancers in the United States, with solar ultraviolet (UV) radiation being a primary etiological factor. T-LAK cell-originated protein kinase (TOPK), a serine/threonine kinase activated by solar UV, has been implicated in skin carcinogenesis. This study aimed to investigate the mechanistic role of TOPK in solar UV-induced skin damage and tumor development. Methods: RNA sequencing (RNA-seq) was performed on skin tissues from wild-type (WT) and TOPK knockout (KO) mice, with or without solar UV exposure, to identify TOPK-regulated genes and pathways. Follow-up experiments using Western blotting, immunofluorescence, and luciferase assays were conducted in vitro and in vivo. Functional assays included 3D spheroid and Transwell co-culture systems involving cutaneous squamous cell carcinoma (cSCC) and fibroblast cells. Results: TOPK deletion altered gene expression profiles and inhibited solar UV-induced activation of multiple signaling pathways, including cytokine–cytokine receptor interaction, PI3K/AKT, MAPKs, PKG, cAMP, and calcium signaling. RNA-seq and protein analyses identified interleukin-19 (IL19) as a key downstream effector suppressed by TOPK deletion. In cSCC and fibroblast cells, TOPK knockdown reduced IL19 expression and secretion. IL19 promoted cSCC growth and activated PI3K/AKT, ERK, and TOPK pathways. Additionally, chronic TGFβ exposure increased IL19 expression and activated fibroblasts, as indicated by elevated αSMA and FAPα levels. Conclusions: These findings establish TOPK as a central regulator of solar UV-induced skin carcinogenesis, partially via modulation of IL19 signaling and fibroblast activation. Targeting TOPK may offer a novel strategy for the prevention and treatment of NMSC. Full article

Background: The opportunistic pathogen Staphylococcus aureus causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the surface of the biofilm, where there is a high concentration of nutrients and oxygen, while in the depths, where these factors are scarce, slowly growing cells remain. Objectives: The aim of our study was to evaluate the antibiofilm potential of ethyl acetate roots (EtOAcR) and aerial parts (EtOAcAP) extracts from the perennial Bulgarian plant Geum urbanum L. against methicillin-resistant S. aureus (MRSA) NBIMCC 8327. Methods: The effects of both extracts on the expression of biofilm-related genes, icaA and icaD, were investigated. The cytotoxicity of EtOAcR and EtOAcAP on A-375 (human melanoma), A-431 (epidermoid skin cancer) and HaCaT (normal keratinocytes) cell lines, and the induction of apoptosis were determined. Finally, the in vivo skin irritation potential of the most active extract was studied. Results: Both tested extracts inhibited biofilm formation at concentrations that did not affect bacterial growth. Interestingly, the expression of icaA and icaD was upregulated, although the biofilm development was inhibited 72.4–90.5% by EtOAcAP and 18.9–20.4% by EtOAcR at sub-MICs. EtOAcAP extract showed a more favorable cytotoxic profile on non-tumorigenic cells and stronger antineoplastic activity (IC₅₀ = 6.7–14.68 µg/mL) as compared to EtOAcR extract (IC₅₀ = 8.73–23.67 µg/mL). Therefore, a skin irritation test was performed with the EtOAcAP extract at ten-times higher concentrations than the minimum inhibitory one, and, resultantly, the primary irritation index was equal to zero (no skin irritation observed). Conclusions: The EtOAcAP extract was proven to be an effective antistaphylococcal agent with favorable skin tolerance. The extract showed strong antineoplastic activity and antibiofilm effect at sub-MICs, which outlines new prospects for its development as a natural product for specific skin applications in medical practice. Full article

Early detection and continuous monitoring of diseases are critical to improving patient outcomes, treatment adherence, and diagnostic accuracy. Traditional melanoma diagnosis relies primarily on visual assessment and biopsy, with reported accuracies ranging from 50% to 90% and significant inter-observer variability. Among emerging diagnostic technologies, Raman spectroscopy has demonstrated considerable promise for non-invasive disease detection, particularly in early-stage skin cancer identification. A portable, real-time Raman spectroscopy system could significantly enhance diagnostic precision, reduce biopsy reliance, and expedite diagnosis. However, miniaturization of Raman spectrometers for portable use faces significant challenges, including weak signal intensity, fluorescence interference, and inherent trade-offs between spectral resolution and the signal-to-noise ratio. Recent advances in silicon photonics present promising solutions by facilitating efficient light collection, enhancing optical fields via high-index-contrast waveguides, and allowing compact integration of photonic components. This work introduces a numerical analysis of an integrated digital Fourier transform spectrometer implemented on a silicon-nitride (SiN) platform, specifically designed for Raman spectroscopy. The proposed system employs a switch-based digital Fourier transform spectrometer architecture coupled with a single optical power meter for detection. Utilizing a regularized regression method, we successfully reconstructed Raman spectra in the 800 cm⁻¹ to 1800 cm⁻¹ range, covering spectra of both benign and malignant skin lesions. Our results demonstrate the capability of the proposed system to effectively differentiate various skin cancer types, highlighting its feasibility as a non-invasive diagnostic sensor. Full article

Background/Objectives: A history of cancer has been linked to stress and concerns about its recurrence. We aimed to test the benefits of an evidence-based self-help stress reduction method, the Clinical Emotional Freedom Technique (EFT), in survivors of cutaneous melanoma, and to contrast its effects on wellbeing and perceptions of cancer recurrence when delivered in a group versus individual instruction setting. Methods: This study was preregistered at clinicaltrials.gov (NCT05421988, 3 April 2022). Fifty-three patients aged 18 and above, diagnosed with melanoma (stage T1a–T2a) at least 6 months prior, and not in active treatment were recruited from a private skin cancer clinic. After consent, all participants were randomized in one step into three condition groups: Group EFT (G-EFT; n = 16), Individual EFT (I-EFT; n = 18), and a waiting-list control condition (CC; n = 19). G-EFT and I-EFT participants attended weekly treatment sessions for four weeks. Perceptions of cancer recurrence and wellbeing measures were obtained pre- and post-intervention and at three-months follow-up using online questionnaires. Subjective units of distress (SUDs) were recorded by the EFT instructor at the beginning and end of each session. Results: Two-way repeated measures ANOVAs revealed significant improvements from pre- to post-intervention in both EFT conditions in terms of participants’ understanding of how to prevent recurrence and in their spiritual wellbeing. No statistically significant effects were found for fear of recurrence, recurrence perceptions, and affect. Significant decreases in SUD scores were observed in both EFT conditions. Over 80% of the experimental conditions’ participants reported positive changes and satisfaction. Conclusions: The findings provide support for offering EFT instruction as a non-pharmacological and noninvasive self-help method to ameliorate the stress of cancer diagnosis and treatment, and for its similar effectiveness in either a group or individual format. Full article

Protein kinase CK2 has emerged as a pivotal regulator of cellular processes involved in skin homeostasis, including cell proliferation, differentiation and inflammatory response regulation. In fact, CK2 activity dysregulation is implicated in the pathogenesis of different skin diseases, such as psoriasis, cancer and inflammatory dermatoses. CK2 overactivation fosters keratinocyte proliferation and pro-inflammatory cytokine production through the STAT3 and Akt pathways in psoriasis, thus contributing to epidermal hyperplasia and inflammation. In the realm of oncology, CK2 overexpression correlates with tumor progression, facilitating cell survival and metastasis in melanoma and non-melanoma skin cancers. Pharmacological inhibition of CK2 has demonstrated therapeutic potential, with CX-4945 (Silmitasertib) as the most studied adenosine triphosphate-competitive inhibitor (ATP-competitive inhibitor). Preclinical models reveal that CK2 inhibitors effectively mitigate pathological features of psoriasis, regulate keratinocyte differentiation, and suppress tumor growth in skin cancers. These inhibitors also potentiate the efficacy of conventional chemotherapeutics and exhibit anti-inflammatory effects in dermatological conditions. Future research will aim to enhance the specificity and delivery of CK2-targeting therapies, including topical formulations, to minimize systemic side effects. Combination therapies integrating CK2 inhibitors with other agents might offer synergistic benefits in managing skin diseases. This review underscores CK2’s critical role in skin and its therapeutic potential as a pharmacological target, advocating for innovative approaches to harness CK2 inhibition in dermatology. Full article

Background/Objectives: Long-term outcome data of locally advanced basal cell carcinoma patients who achieve complete response (CR) on hedgehog pathway inhibitors (HHIs) are lacking, highlighting a gap in the identification of the predictors of tumor recurrence. We aimed to investigate the clinical and histological factors associated with locally advanced BCC recurrence after CR on HHIs. Patients and methods: We performed a retrospective multicenter observational study at 14 Italian tertiary referral centers (1 January 2016–1 March 2024). Univariate logistic regression was used to investigate the association between locally advanced BCC recurrence and clinical and histological features. Kaplan–Meier analysis was used to estimate relapse-free survival (RFS). Results: A total of 106 locally advanced BCC patients were enrolled, of whom 14/106 (13.2%) experienced relapse after a median follow-up of 12 months (range: 1–70 months). Low-risk locally advanced BCC histological subtypes (superficial and nodular) were associated with a decreased probability of locally advanced BCC recurrence (odds ratio [OR]: 0.15, 95% CI: 0.04–0.51; p: 0.003); a longer time to CR predicted locally advanced BCC relapse (OR: 1.07, 95% CI: 1.01–1.15; p: 0.04). Accordingly, locally advanced BCC histology and time to CR significantly impacted RFS probability. Conclusions: Specific locally advanced BCC histological subtypes and time to CR predict tumor recurrence after CR on HHIs. Full article

Janus kinase inhibitors, including tofacitinib, filgotinib, and upadacitinib, have emerged as effective therapeutic options for the management of inflammatory bowel diseases (IBDs). By targeting the JAK-STAT signaling pathway, these agents modulate immune responses and reduce inflammation. However, concerns regarding the potential risk of malignancy associated with their use have gained significant attention. The JAK-STAT pathway is not only critical for inflammatory signaling but also plays a pivotal role in cellular growth, differentiation, and tumor surveillance. Observational studies and clinical trial data in rheumatoid arthritis have reported malignancies, including non-melanoma skin cancer and solid tumors, in patients receiving JAK inhibitors, with evidence suggesting variable risks depending on the selectivity of the agent. Current evidence does not suggest an increased risk of oncogenesis in patients with IBDs. Balancing therapeutic efficacy with long-term safety requires ongoing vigilance; patient stratification based on risk factors; and tailored monitoring strategies to mitigate potential adverse effects, including malignancies, during JAK inhibitor therapy. Long-term follow-up data of up to 10 years offer reassuring evidence that JAK inhibitor therapy in IBD patients does not confer an increased risk of malignancies, supporting their continued use within appropriate clinical settings. Full article