Search Results (474)

The incidence of melanoma is increasing globally, even in the wake of increased risk factor awareness and a growing body of advanced therapeutic options. It is apparent that the treatment of melanoma will remain a topic of worry in areas of the world under high ultraviolet exposure and areas that harbor individuals with fair skin phenotypes. In the wake of such concern, the potential of immunotherapy and various targeted therapeutics to treat late-stage melanoma is increasing. In addition to the growing arsenal of PD-1 and PD-L1 immune checkpoint inhibitors, other targeted therapies are being developed and tested to treat melanoma. BRAF/MEK inhibitors target a key proliferative pathway in melanoma, offering clinical benefit but limited durability. Next-generation agents and triplet therapy with immunotherapy aim to improve outcomes. Androgen receptor signaling may also modulate responses to both targeted and immune-based treatments. Bispecific T cell engagers assist with guiding the body’s own T cells to tumors where they release toxins that kill the tumor cell. Personalized neoantigen vaccines target tumor-specific antigens by sequencing a patient’s cancerous cells to create tailored vaccines that elicit a strong and specific immune response. Tumor-infiltrating lymphocytes are autologous lymphocytes reinfused back into the host that are showing efficacy in the treatment of advanced melanoma. Together, these therapies are advancing the arsenal of chemotherapeutic options that can be used to inhibit the progression of melanoma. Full article

Background: Melanoma is a malignant tumor of melanocytes with an increasing incidence worldwide. Plant-based products are rich in bioactive compounds, offering low toxicity and accessible alternatives for melanoma treatment. A biotechnological approach to obtaining plant-derived produce ensures continuous and high-yield production of medicinally valuable biomass. Objectives: This study aimed to induce and optimize the growth of homogenous callus cultures of Kickxia elatine (L.) Dumort., consequently established a cell suspension culture with a high biomass growth rate, analyzed the phytochemical compositions, and assessed the cytotoxic activity against melanoma cells. Methods/Results: Callus cultures were induced under controlled in vitro conditions on Murashige and Skoog (MS) media supplemented with 2.0 mg L⁻¹ Dicamba and 2.0 mg L⁻¹ 2,4-Dichlorophenoxyacetic acid. The selected callus lines exhibited a high growth index (351.71% ± 27.77) and showed a homogeneous morphology, beige colour, and had friable and watery characteristics. A combination of auxin and cytokinin was found to enhance biomass production significantly. Phytochemical investigations putatively annotated major compounds, including benzoic acid derivatives, phenolic glycosides, phenylpropanoic acids, hydroxycinnamic acid derivatives, and tyrosol derivatives. Methanolic extract (KE-Ex) and 40% methanolic fraction (KE-40Fr) were prepared and tested for cytotoxicity against human fibroblast (MRC-5) and melanoma (MeWo) cell lines using direct cell counting and MTT assay. The crude extract exhibited the strongest cytotoxicity effect on MeWo cells, with IC₅₀ values of 125 ± 8 µg mL⁻¹ after 48 h and 117 ± 7 µg mL⁻¹ after 72 h of treatment. Conclusions: The extract demonstrated a time- and dose-dependent cytotoxic effect, making it a potential candidate for melanoma treatment. Full article

Melanoma is an aggressive cutaneous malignancy with increasing global incidence and high metastatic potential. While ultraviolet (UV) radiation remains the primary environmental risk factor, emerging evidence suggests that dietary factors may influence melanoma risk, progression, and treatment outcomes. This comprehensive review examines the impact of dietary components, including fats, vitamins, minerals, antioxidants, bioactive compounds, and the gut microbiome, on melanoma pathogenesis. The current literature indicates that diets rich in polyunsaturated fatty acids (PUFAs), antioxidants, and plant-based bioactive compounds may confer protective effects against melanoma by modulating oxidative stress, inflammation, and immune response. Additionally, the gut microbiome plays a critical role in melanoma progression and immunotherapy response, with dietary patterns influencing microbial composition and, consequently, host immunity. Despite these promising associations, research remains limited, and findings across studies are inconsistent, preventing the establishment of definitive dietary guidelines for melanoma prevention and management. Future research should focus on large-scale prospective studies to elucidate the mechanisms underlying the dietary influences on melanoma and determine evidence-based nutritional strategies. Understanding the interplay between diet, immune modulation, and gut microbiome composition represents a promising avenue for advancing melanoma prevention and treatment strategies. Full article

Melanoma has important burden in older populations due to high incidence and aggressive biology. The emergence of immunotherapy with immune checkpoint inhibitors and targeted therapy (BRAF/MEK inhibitors) significantly improved melanoma prognosis. Currently, the body of knowledge on the efficacy and tolerability of these treatments in geriatric patients is primarily based on the results outside of clinical trials since the majority of clinical studies do not include older patients. We present a comprehensive narrative review of published data regarding efficacy and safety of therapeutic modalities using immune checkpoint inhibitors in patients age 65–75 years and >75 years: the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor (ipilimumab), the anti-programmed death-ligand 1 (PD-1) inhibitors (nivolumab and pembrolizumab), and the lymphocyte activation gene-3 (LAG-3) inhibitor (relatlimab). We carefully address difficulties in multi-disciplinary clinical decision-making in care of older melanoma patients. Although many older patients may not be offered immunotherapy, the available evidence indicates that immunotherapy is equally beneficial in the older patients and does not have higher incidence of adverse events in this group of patients compared to younger population. Full article

Background/Objectives: Melanoma has a rising incidence worldwide. Current treatments are effective, although the development of resistance is common. A novel anti-cancer treatment using checkpoint kinase 1 inhibitor (CHK1i), SRA737, in combination with low-dose hydroxyurea (LDHU), has been demonstrated to effectively kill tumour cells and promote an anti-tumour immune response through the treatment-induced release of pro-inflammatory chemokines and cytokines. These chemokines/cytokines modify the tumour microenvironment from an immunosuppressive to an inflamed state to recruit anti-tumour immune cells. Methods: A panel of human melanoma cell lines was assessed using a panel of chemokines and cytokine expression, and the mechanism of their regulation was investigated. Results: We demonstrate that SRA737 + LDHU upregulates pro-inflammatory chemokines in human melanoma cells in response to SRA737 + LDHU through the ATM-NF-κB signalling pathway. The increased chemokine expression corresponded to the increase in secretion of pro-inflammatory chemokines from tumour cells following SRA737 + LDHU treatment. However, inhibiting NF-κB and ATM did not affect SRA737 + LDHU-induced cell killing. Increased expression of non-NF-κB target genes with SRA737 + LDHU suggests that other transcriptional pathways are also activated and may contribute to the increasing cytokine/chemokine gene expression in response to treatment. Conclusions: SRA737 + LDHU upregulates pro-inflammatory chemokine expression through an ATM-NF-κB-dependent mechanism. Full article

Background: With its incidence on the rise, a high mortality rate, and great costs associated with its treatment, melanoma represents an important challenge for healthcare systems, clinicians, and pathologists. Therefore, an emphasis should be placed on its early and correct diagnosis, as well as the appropriate assessment of prognostic and predictive factors. Immunohistochemistry (IHC) is an ancillary test that can provide invaluable information for diagnosing melanoma, especially in complex cases. Objective: The aim of this systematic review is to gather the available information regarding the use of IHC markers in the diagnosis, differential diagnosis, prognosis, staging, and treatment of melanoma in a format that is easy to access for clinicians and pathologists. Methods: A comprehensive search of the literature was conducted and resulted in one hundred and forty-seven studies being included in this systematic review. The results were grouped thematically by specific IHC markers. Results: The IHC markers specific to melanocytic differentiation, like S100, SOX10, and Melan-A/MART1, were consistent across studies as being positive in most cases of melanoma, with rare exceptions. HMB-45 and PRAME can provide additional information, especially for differential diagnoses between benign and malignant melanocytic lesions. MITF, Ki67, BRAF, and PD-L1 are associated with prognosis factors, like the Breslow thickness, tumour ulceration, type of inflammatory infiltrate, and response to treatment. Conclusions: IHC markers are an invaluable tool for the diagnosis and differential diagnosis of melanoma, especially in cases that lack the characteristic histopathological aspects. In addition, IHC provides prognostic factors and can help in predicting the tumour’s response to various treatments. Full article

Introduction: The introduction of biologic therapies and small molecule drugs has revolutionized the management of inflammatory bowel disease (IBD), providing targeted control of inflammation. However, concerns remain regarding their long-term safety profiles, particularly in relation to cancer risk. Chronic inflammation and immunosuppressive therapies contribute to malignancy risk, including skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This review examines the evidence on skin cancer risks associated with these therapies, focusing on specific drug classes and their mechanisms. Results: Tumor necrosis factor (TNF) inhibitors have shown conflicting evidence regarding melanoma risk, with some studies reporting a modest increase and others finding no significant association. Anti-integrin agents, such as vedolizumab, and interleukin (IL)-12/23 inhibitors, including ustekinumab, have demonstrated favorable safety profiles with minimal skin cancer risks. Selective IL-23 inhibitors and sphingosine-1-phosphate (S1P) receptor modulators have limited long-term data, but early findings indicate a low incidence of skin malignancies. Janus kinase (JAK) inhibitors do not show an increased risk of skin cancers in IBD. Conclusions: Current evidence suggests that skin cancer risk in IBD patients treated with biologics and small molecule drugs varies by drug class. TNF inhibitors and JAK inhibitors are associated with higher risks, while other therapies show lower malignancy risks. Regular skin cancer screening and protective measures remain critical, particularly for patients with additional risk factors. Further long-term studies are essential to refine safety profiles and inform clinical practice in this evolving therapeutic landscape. Full article

Melanoma incidence is increasing, with distinct genetic and clinical patterns observed in the Latin American population. This study aimed to evaluate melanoma risk in a Colombian cohort through polygenic risk analysis using 37 variants across nine genes previously associated with melanoma. We performed polygenic risk score (PRS) analysis on 85 melanoma patients and 165 controls. Genotyping was performed for 37 melanoma-associated SNPs, and on the basis of previous GWAS reports, individual PRSs were calculated for each participant. The participants were then stratified into quartiles to examine risk gradients. In addition, phenotypic features such as eye and hair color were evaluated, and genetic models and haplotype analyses were performed, adjusting for sex and family history of cancer. PRS quartile stratification revealed a clear risk gradient. Notably, 31.8% of the melanoma cases were clustered in the highest-risk quartile (Q4), with a maximum PRS of 1.04. Variants in TYR, TYRP1, CDKN2A, and HERC2 significantly contributed to risk, and light brown eye and hair colors were strongly associated with increased melanoma risk. Moreover, a protective haplotype in the OCA2-HERC2 region was identified among males. The integration of the PRS with clinical and phenotypic factors has potential for improving melanoma risk stratification in the Colombian population, warranting further investigation in larger, diverse cohorts. Full article

Background/Objectives: Malignant melanoma (MM) is an aggressive neoplasm with a rising global incidence. Accurate staging and risk stratification are essential for guiding therapeutic decisions and improving patient prognosis. [18F]-FDG PET-CT enables the non-invasive assessment of tumor metabolic activity, offering a valuable adjunct to histopathological evaluation. However, the correlation between PET-CT findings and established prognostic markers in MM, such as Breslow thickness, ulceration, and mitotic rate, remains insufficiently explored. Methods: This retrospective observational study included 61 patients diagnosed with MM, of whom 48 met the inclusion criteria. Quantitative and qualitative variables such as SULmax, Breslow thickness, Ki-67 expression, and mitotic rate were analyzed using descriptive statistics, while correlations between PET-CT findings, SLNB, and histopathological characteristics were assessed using Spearman’s correlation test. A p-value < 0.05 was considered statistically significant. Results: Significant associations were identified between ulceration and both overall metastases (p = 0.01) and pulmonary metastases (p = 0.02). Breslow thickness showed a positive correlation with metastatic spread (p = 0.01), reinforcing its role as a key prognostic indicator. Perineural and vascular invasion were significantly associated with intra-abdominal metastases (p < 0.001 and p = 0.0007, respectively). Tumor-infiltrating lymphocytes (TILs) were inversely correlated with intra-abdominal metastases (p = 0.05), while sentinel lymph node positivity correlated with the presence of regional (p = 0.008) and distant (p = 0.02) metastases. Additionally, subcutaneous SULmax values were significantly higher in male patients compared to females (p = 0.04). Conclusions: Integrating PET-CT metabolic parameters with histopathological markers enhances the assessment of MM aggressiveness and metastatic potential. By refining risk stratification, PET-CT may contribute to personalized therapeutic strategies and improved patient management in MM. Full article

Melanoma is one of the deathliest cancers worldwide and its incidence is reaching epidemic proportions. It is characterized by intrinsic chemo-resistance, low response rates to treatment and high metastatic potential. Because of this, new therapeutic options are permanently required. Tessaria absinthioides (Hook. & Arn.) DC. is a traditional medicinal plant, with antioxidant, selective cytotoxicity and anti-colorectal cancer evidence-based properties. This study aims to demonstrate the antitumoral and antimetastatic effects of T. absinthioides decoction (DETa), correlating in vitro and in vivo activities in a murine melanoma model. DETa was assayed on B16F0 murine non-metastatic cells to determine cytotoxicity and clonogenicity; while, in the B16F10 metastatic siblings, adhesion, wound healing migration and Boyden chamber invasion were studied. The ex vivo intestinal-sac model was used to quantify DETa bioavailability. Meanwhile, in C57BL6/wt mice, DETa was orally administered to evaluate its antitumoral and antimetastatic activities. DETa induced cytotoxicity in a dose- and time-dependent manner, affecting the long-term clonogenic survival, as well as the processes of adhesion and migration. Then, the intestinal absorption of DETa phenolics was proven, while the systemic anti-tumoral and anti-metastatic activities of DETa were confirmed. Results demonstrated that DETa has antimelanoma activity promoting this botanical compound as a relevant agent for cancer research and treatment. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) face an increased risk of developing intestinal and extraintestinal cancers. This retrospective single-center study aimed to quantify cancer risk and identify potential risk factors associated with cancer in IBD patients. Methods: The epidemiological data, disease characteristics, treatment regimens, and occurrences of cancer following IBD diagnosis were collected between January 2021 and February 2022. Hazard ratios (HRs) and standardized incidence ratios (SIRs) were estimated. Results: 560 IBD patients were included; 37 patients developed cancer, with 5 patients developing two distinct cancers, resulting in 42 cancers overall. This translated into a twofold increased risk of developing any cancer compared to the general population (SIR 1.94, 95% CI 1.4–2.6). Colorectal (CRC, 29%), skin (19%), and breast cancer (17%) were the most common malignancies. Female patients showed an increased risk for all cancers (SIR 3.1, 95% CI 2.06–4.3), melanoma (SIR 5.6, 95% CI 1.14–16.2), and CRC (SIR 7.5, 95% CI 3–15.4). Conversely, male patients exhibited a significantly increased risk of lymphoma (SIR 26.2, 95% CI 3.2–95.7). Young age at IBD diagnosis and the use of immunomodulators, whether as monotherapy or in combination with biologics, were associated with an increased risk of cancer. Conclusions: The risk of CRC and lymphoma in IBD patients may be higher than previously reported, potentially due to the increasing use of combination therapy. Cancer risk in IBD should be regularly assessed and personalized throughout the disease course. Full article

Background: Uveal melanoma (UM) is a rare subtype of melanoma with distinct clinical and molecular features compared to other melanoma subtypes. UM tumors are frequently detected with mutations in GNA11, GNAQ, EIF1AX, BAP1, and SF3B1 instead of the typical mutations associated with cutaneous melanoma. Although hereditary UM is rare, germline BAP1 loss predisposes patients to UM and various other cancers. The CHEK2 (Checkpoint kinase 2) gene that encodes the protein CHK2, a serine-threonine kinase, is a cell cycle checkpoint regulator that acts as a tumor suppressor. CHK2 is involved in DNA repair, cell cycle arrest, or apoptosis in response to DNA damage. CHEK2 mutations have been linked to various cancers. While there is no strong evidence that CHEK2 mutations increase the risk of melanoma, two cases of germline CHEK2 mutations in UM patients have been reported. However, the incidence of CHEK2 variants in metastatic UM (MUM) has not been investigated. Thus, we conducted a retrospective analysis of patients with MUM and CHEK2 variants to understand this link better. Methods: We collected MUM cases from 2016 to 2024 from institutional databases. Tissues underwent analyses of molecular and genomic features, including tumor mutational burden, and were performed by a Clinically Certified Laboratory. Next-generation sequencing and variant calling were conducted to identify CHEK2 variants. Results: In this study, we reported ten patients with CHEK2 variants among 740 metastatic UM patients (1.4%) and four primary UM patients with CHEK2 germline mutations. Conclusions: Although rare, UM patients with an abnormal ATM–CHEK2 axis might receive clinical benefits from medications that target DNA repair mechanisms. Full article

Background: The incidence of malignant melanoma (MM) continues to increase annually, and tumour invasiveness is a main prognostic factor. Single-nucleotide polymorphisms (SNPs) have become key tools in the study of cancer genetics, influencing susceptibility and prognosis. Methods: In the present study, we analysed the relationship between five SNPs on the PDCDL1 gene (rs822336, rs822337, rs822338, rs229736, rs4143815) with prognosis as well as primary tumour invasiveness characteristics in 377 whole blood samples from MM individuals. Results: Patients who presented the rs822336 CG or GG genotypes (OR = 3.01, 95% CI = 1.53–5.92; p = 0.0017), TA or TT in rs822337 (OR = 2.45, 95% CI = 1.22–4.93; p = 0.0098), and CT or CC of rs822338 (OR = 2.23, 95% CI = 1.05–4.73; p = 0.028) were at an increased risk of developing invasive melanomas. Cases with the AG or GG genotype in rs2297136 presented a lower risk (OR = 0.29, 95% CI = 0.11–0.75; p = 0.0038) of invasive MM. The genetic analysis at the haplotype level resulted in similar findings (OR: 2.95, 95% CI: 1.08–8.10), p = 0.036). Furthermore, patients carrying the homozygous AA genotype in rs2297136 had thicker tumours than those harbouring the AG or GG (1.4 mm vs. 1.0 and 0.8 mm; p = 0.030). No significant association was found between the studied SNPs and melanoma-specific survival (MSS) nor progression-free survival (PFS). Conclusions: Current results suggest that SNPs rs822336, rs822337, rs822338, and rs2297136 genotypes in the PDCDL1 gene are associated with the risk of tumour invasiveness and tumour thickness in MM. Further studies on SNPs considering genetic and epigenetic factors are needed for a better understanding of malignant melanoma susceptibility and its prognosis. Full article

Melanoma is an aggressive cancer with rising incidence, particularly among older individuals. Despite advancements in targeted therapies for BRAF and MEK proteins and immunotherapies, many patients either fail to respond or develop resistance. For those progressing on immunotherapy, limited treatment options remain. The Cyclin D–CDK4/6–RB pathway is commonly dysregulated in melanoma, with up to 90% of cases showing alterations that activate it. Although targeting Cyclin–CDK complexes has shown promise in preclinical models, clinical responses have been suboptimal. This review explores the molecular mechanisms behind Cyclin–CDK dysregulation in melanoma and the challenges of targeting this pathway. It also discusses strategies to improve the efficacy of CDK4/6 inhibitors, including combination therapies to overcome resistance and enhance patient outcomes. Understanding these mechanisms can guide the development of more effective treatments for melanoma. Full article

Background/Objectives: The increasing incidence of cancer during pregnancy is a growing public health concern, driven by delayed parenthood and rising maternal age. Pregnancy-associated cancer (PAC) presents complex clinical challenges, necessitating a balance between maternal cancer treatment and fetal safety. Historically considered incompatible with favorable pregnancy outcomes, evidence now suggests that pregnancy can often proceed without affecting cancer prognosis. A 2022 study in Italy provided the first population-based PAC estimates by linking cancer registries (CRs) and hospital discharge records (HDRs). This study aimed to update PAC estimates to 2019, covering 30% of the Italian population and addressing prior data limitations. Methods: A retrospective longitudinal analysis was conducted on women aged 15–49 diagnosed with malignant cancers between 2003 and 2019. Data from 21 Italian CRs were linked with HDRs to identify PAC cases, defined as obstetric hospitalizations occurring for women diagnosed with cancer in our study cohort in the period spanning from one year before to two years after a cancer diagnosis. All malignant cancers, excluding non-melanoma skin cancers, were analyzed. PAC rates were calculated per 1000 pregnancies, and trends were assessed using log-linear and JoinPoint regression models. Results: Among 131,774 women diagnosed with cancer, 6329 PAC cases were identified, with a PAC rate of 1.43 per 1000 pregnancies, consistent with global estimates. Thyroid (24.4%) and breast cancer (23.2%) were the most common. Analyzing the PAC rate by pregnancy outcome, in the period 2015–2019, this increased for both childbirths and miscarriages but decreased for voluntary terminations. Most hospitalizations (54%) occurred pre-diagnosis, peaking at diagnosis, especially for breast cancer (69%). Conclusions: PAC incidence is rising, particularly for live births and miscarriages, underscoring the need for multidisciplinary care and robust epidemiological insights to guide clinical management. Full article