Metastatic melanoma remains a devastating disease with a 5-year survival rate of less than five percent. Despite recent advances in targeted therapies for melanoma, only a small percentage of melanoma patients experience durable remissions. Therefore, it is critical to identify new therapies for the treatment of advanced melanoma. Here, we define connective tissue growth factor (CTGF) as a therapeutic target for metastatic melanoma. Clinically, CTGF expression correlates with tumor progression and is strongly induced by hypoxia through HIF-1 and HIF-2-dependent mechanisms. Genetic inhibition of CTGF in human melanoma cells is sufficient to significantly reduce orthotopic tumor growth, as well as metastatic tumor growth in the lung of severe combined immunodeficient (SCID) mice. Mechanistically, inhibition of CTGF decreased invasion and migration associated with reduced matrix metalloproteinase-9 expression. Most importantly, the anti-CTGF antibody, FG-3019, had a profound inhibitory effect on the progression of established metastatic melanoma. These results offer the first preclinical validation of anti-CTGF therapy for the treatment of advanced melanoma and underscore the importance of tumor hypoxia in melanoma progression.
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http://dx.doi.org/10.1038/onc.2013.47 | DOI Listing |
Am J Rhinol Allergy
January 2025
Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.
Background: Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma.
Objective: We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma.
Fluids Barriers CNS
January 2025
Department of Anatomy, Cellular and Molecular Neurobiology Research Group, Faculty of Medicine, Masaryk University, 625 00, Brno, Czech Republic.
Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3-10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20-56%), breast (5-20%), and melanoma (7-16%) tumors, although they can arise from other cancer types less frequently.
View Article and Find Full Text PDFNat Commun
January 2025
IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch Cedex, C.U. Equipe Labélisée Ligue contre le Cancer, Strasbourg, France.
The plasticity of cancer cells facilitates their ability to adopt heterogeneous differentiation states, posing a significant challenge to therapeutic interventions. Specific gene expression programs, driven in part by super-enhancers (SEs), underlie cancer cell states. Here we successfully inhibit SE-driven transcription in phenotypically distinct metastatic melanoma cells using next-generation synthetic ecteinascidins.
View Article and Find Full Text PDFJ Cutan Pathol
January 2025
Stritch School of Medicine, Loyola University, Maywood, Illinois, USA.
Metastatic melanoma with unusual histopathology can be diagnostically challenging. One exceptionally rare cutaneous manifestation of metastases is blue-nevus-like metastatic melanoma (BNLMM). A 74-year-old male presented with a blue-gray lesion on his left helix in the same anatomical region of a previously resected lentigo maligna.
View Article and Find Full Text PDFMelanoma Res
January 2025
UOC di Patologia Clinica, San Giovanni Bosco Hospital, ASLNa1Centro, Napoli, Italy.
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