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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.
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http://dx.doi.org/10.3390/cancers17081291 | DOI Listing |
EMBO J
September 2025
School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Insulin resistance is a heritable risk factor for many chronic diseases; however, the genetic drivers remain elusive. In seeking these, we performed genetic mapping of insulin sensitivity in 670 chow-fed Diversity Outbred in Australia (DOz) mice and identified a genome-wide significant locus (QTL) on chromosome 8 encompassing 17 defensin genes. By taking a systems genetics approach, we identified alpha-defensin 26 (Defa26) as the causal gene in this region.
View Article and Find Full Text PDFAerosp Med Hum Perform
September 2025
Introduction: Pilots have an increased incidence of cutaneous melanoma compared to the general population; occupational exposure to ultraviolet (UV) radiation is one of several potential risk factors. Cockpit windshields effectively block UVB (280-315 nm) but further analysis is needed for UVA (315-400 nm). The objective of this observational study was to assess transmission of UVA through cockpit windshields and to measure doses of UVA at pilots' skin under daytime flying conditions.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
School of Life Sciences, Anhui Medical University, Hefei, 230032, China; Translational Research Institute of Henan Provincial People's Hospital, Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metaboli
Melanoma is the most aggressive and lethal form of skin cancer, posing significant challenges for prognosis assessment and treatment. Recently, metabolic reprogramming and epigenetic regulation have gained attention for their roles in cancer progression. The role of the key metabolic enzyme dihydrolipoic acid succinyltransferase (DLST) in cancer is currently unclear.
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September 2025
Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200000, China; Academy for Clinical Innovation and Translation of Shanghai, Shanghai 200000, China. Electronic address:
Background: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) with rapidly progressive interstitial lung disease (RPILD) is a fatal disease. Although Janus kinase inhibitors (JAKi) hold their promise in treating MDA5+ DM, regimen for RPILD is still urgently needed to improve the adverse prognosis.
Methods: Based on a large inception cohort of MDA5+ DM, patients with RPILD (oxygen index [OI] < 300 within the first 3 months of disease duration) were included.
Biomaterials
September 2025
Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:
The stimulator of interferon genes (STING) pathway represents a promising target in cancer immunotherapy. However, the clinical translation of cyclic dinucleotide (CDN)-based STING agonists remains hindered by insufficient formation of functional CDN-STING complexes. This critical bottleneck arises from two interdependent barriers: inefficient cytosolic CDN delivery and tumor-specific STING silencing via DNA methyltransferase-mediated promoter hypermethylation.
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