Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance.

Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR).

Educational level-dependent melanoma awareness in a high-risk population in Switzerland.

Introduction: The worldwide incidence of melanoma has been increasing rapidly in recent decades with Switzerland having one of the highest rates in Europe. Ultraviolet (UV) radiation is one of the main risk factors for skin cancer. Our objective was to investigate UV protective behavior and melanoma awareness in a high-risk cohort for melanoma.

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs.

Over-Detection of Melanoma-Suspect Lesions by a CE-Certified Smartphone App: Performance in Comparison to Dermatologists, 2D and 3D Convolutional Neural Networks in a Prospective Data Set of 1204 Pigmented Skin Lesions Involving Patients' Perception.

The exponential increase in algorithm-based mobile health (mHealth) applications (apps) for melanoma screening is a reaction to a growing market. However, the performance of available apps remains to be investigated. In this prospective study, we investigated the diagnostic accuracy of a class 1 CE-certified smartphone app in melanoma risk stratification and its patient and dermatologist satisfaction.

Collection and preprocessing of fine needle aspirate patient samples for single cell profiling and data analysis.

High cell viability and recovered cell concentration are typical quality control requirements for single-cell processing and quality data. This protocol describes procedures for sampling, live-cell biobanking, preprocessing for single-cell RNA sequencing, and analysis of fine-needle aspiration (FNA) samples of the skin. The minimally invasive nature of FNA collection is more accepted by patients and allows for frequent longitudinal sampling, resulting in high-quality single-cell sequencing data that capture cellular heterogeneity in clinical samples.

Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective.

Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex 1 virus (HSV-1) approved for cancer therapy. We investigate its effect on the clinical, histological, single-cell transcriptomic, and immune repertoire level using repeated fine-needle aspirates (FNAs) of injected and noninjected lesions in primary cutaneous B cell lymphoma (pCBCL). Thirteen patients received intralesional T-VEC, 11 of which demonstrate tumor response in the injected lesions.

Targeting complex, adaptive responses in melanoma therapy.

Our understanding of the complex, adaptive mechanisms of response to targeted therapies in metastatic melanoma is now leading to more effective combination treatments. These include the simultaneous inhibition of signalling pathways and metabolic programmes, as well as epigenetic mechanisms or immunological checkpoints. We review the latest pre-clinical and clinical results of strategies to delay tumor progression through combination approaches, and also highlight some of the problems ahead, including patient stratification, the complexity of targeting adaptive responses, and the management of more severe toxicities that result from double and triple-drug treatments.

miR-181a decelerates proliferation in cutaneous squamous cell carcinoma by targeting the proto-oncogene KRAS.

Cutaneous squamous cell carcinoma (SCC) is the second most common human skin cancer with a rapidly increasing incidence among the Caucasian population. Among the many regulators, responsible for cancer progression and growth, microRNAs (miRNA) are generally accepted as key players by now. In our current study we found that microRNA-181a (miR-181a) shows low abundance in SCC compared to normal epidermal skin.

Epigenetic impacts of ascorbate on human metastatic melanoma cells.

In recent years, increasing evidence has emerged demonstrating that high-dose ascorbate bears cytotoxic effects on cancer cells in vitro and in vivo, making ascorbate a pro-oxidative drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. This anticancer effect of ascorbate is hypoxia-inducible factor-1α- and O2-dependent. However, whether the intracellular mechanisms governing this effect are modulated by epigenetic phenomena remains unknown.

Auxin responses in mutants of the Arabidopsis CONSTITUTIVE PHOTOMORPHOGENIC9 signalosome.

The CONSTITUTIVE PHOTOMORPHOGENIC9 (COP9) signalosome (CSN) is an evolutionarily conserved multiprotein complex that interacts with cullin-RING type E3 ubiquitin ligases (CRLs). CSN subunit 5 (CSN5), which, when incorporated into CSN, can deconjugate the NEDD8 modification from the cullin subunit of CRLs, is essential for CSN's role in controlling CRL activity. Whether the CSN5 monomer, which is maintained in csn mutants such as csn3 or csn4, has a functional role, remains to be established.