Skin cancer prevalence has increased during the last decades, with the last years serving as a pivotal moment for comprehending its epidemiological patterns and its impact on public health. Melanoma is one of the most frequently occurring malignancies, arising from a complex interplay of genetic factors, environmental factors, lifestyle and socio-economic conditions. Epigenetic changes play a critical role in tumor development, influencing progression and aggressiveness. Epigenetic therapies could represent novel therapeutic options, while drug repositioning may serve as a viable strategy for cancer treatment. Demethylating agents, commonly used in hematological malignancies, show promising results on solid tumors, including melanoma. Methylation patterns are responsible for tumor development by modulating gene expression, while histone acetylation influences DNA processes such as transcription, replication, repair, and recombination. This review aims to identify existing potential therapeutical approaches using therapeutic agents that can modulate DNA methylation and histone modification, which can lead to tumor inhibition, cell death initiation and reactivation of tumor suppressor genes.

Proteolysis-targeting chimeras (PROTAC) leverage the ubiquitin–proteasome system to selectively degrade oncogenic proteins, including those previously seen as undruggable. Recent preclinical studies indicate that PROTACs may represent a novel therapeutic strategy in lymphoma and myeloma. Indeed, preclinically, PROTACs have shown high efficacy and remarkable selectivity, a favorable safety profile, and lower toxicity compared with conventional therapies. Their catalytic, reusable mechanism enables drug dosing and offers the perspective of long-term low-dose treatment. PROTACs have demonstrated their ability to overcome drug resistance by targeting and degrading overexpressed or mutant proteins that are responsible for refractory disease. This review aims to offer a comprehensive evaluation of the currently existing PROTACs that have been tested in lymphoma and myeloma to highlight the need for drug optimization and further translational research that could translate PROTACs to clinical trials.

Background and Objectives: Traditional open anterior cruciate ligament transection (ACLT) surgical models performed through arthrotomy may introduce capsular trauma and postoperative inflammatory responses that can interfere with the interpretation of post-traumatic osteoarthritis (OA). This study aimed to evaluate the feasibility of a minimally invasive, arthroscopic ACLT rabbit model performed entirely under arthroscopic visualization, without arthrotomy, using a 2.4-mm arthroscope and 2.5-mm shaver, and to provide preliminary structural, histological, synovial, and systemic biochemical characterization of the model for future therapeutic testing. Materials and Methods: Bilateral arthroscopic ACLT was performed in three skeletally mature New Zealand rabbits, followed by a supervised 12-week exercise protocol. Joint degeneration was evaluated macroscopically and histopathologically using the standardized Pritzker-Osteoarthritis Research Society International (OARSI) grading system. Collagen matrix remodeling was assessed via Picrosirius Red staining. Local intra-articular catabolism was quantified via Enzyme-Linked Immunosorbent Assay (ELISA) for matrix metallopeptidase 13 (MMP-13) and interleukin-1β (IL-1β) from synovial fluid. Systemic oxidative stress, including lipid peroxidation biomarkers, malondialdehyde (MDA), and nitric oxide (NO), was evaluated in serum. Results: The arthroscopic approach induced osteoarthritic changes, with severity varying across the cohort. Histopathology revealed vertical matrix fissures and disruption of the normal columnar chondrocyte organization, yielding a median comprehensive Pritzker-OARSI score of 6 (range 6–10), with horizontal degradation restricted to stage 2. Synovial fluid analysis demonstrated measurable concentrations of MMP-13 (188.77 ± 93.87 ng/mL) and IL-1β (174.93 ± 95.51 pg/mL). Furthermore, serum oxidative stress parameters at the 12-week endpoint included lipid peroxidation (MDA: 1.01 ± 0.03 nmol/mL) and NO levels (82.72 ± 0.32 µmol/L), presented descriptively in the absence of a comparator group. Conclusions: This study establishes the first multifaceted pathological baseline of a minimally invasive arthroscopic ACLT rabbit model before therapeutic intervention. The arthroscopic ACLT model produced structural cartilage degeneration alongside measurable intra-articular catabolic and systemic oxidative stress changes, establishing a baseline phenotype and a starting point for future therapeutic studies.