Fyn is a non-receptor tyrosine kinase belonging to the Src family kinases. It has been shown to play important roles in neuronal functions, including myelination and oligodendrocytes formation, and in inflammatory processes. It has also demonstrated its involvement in signaling pathways that lead to severe brain pathologies, such as Alzheimer's and Parkinson's diseases. Moreover, Fyn is upregulated in some malignancies. Experimental studies demonstrated that Fyn inhibition could be useful in the disruption of metabolic processes involved in cancer neurodegenerative diseases. Unfortunately, no specific Fyn inhibitor has been discovered till today, active compounds on other members of Src family or on different tyrosine kinases have also been reported. However, multitargeted inhibitors might be endowed with therapeutic potential. Indeed, as increasingly reported, also a not completely selective inhibitor of a specific protein could be therapeutically useful, affecting a number of cell pathways involved especially in cancer development. In this review, we report some examples of small molecule tyrosine kinase inhibitors for which data on Fyn inhibition, both in enzymatic and in cell assays, have been reported, with the aim of giving information as starting point for the researchers working in this field.
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http://dx.doi.org/10.2174/092986711796150531 | DOI Listing |
Acta Pharmacol Sin
January 2025
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
The emergence of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the prognosis for lung cancer patients with EGFR-driven mutations. However, acquired resistance to EGFR-TKIs poses a significant challenge to the treatment. Overcoming the resistance has primarily focused on developing next-generation targeted therapies based on the molecular mechanisms of resistance or inhibiting the activation of bypass pathways to suppress or reverse the resistance.
View Article and Find Full Text PDFBlood Cancer J
January 2025
School of Medicine, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Fedratinib is a predominantly JAK2 inhibitor that has shown efficacy in untreated and ruxolitinib-exposed patients with myelofibrosis (MF). Based on randomized clinical trial data, it is approved for use in patients with International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk disease and is distinguished from ruxolitinib in that it can be administered without dose reduction in patients with thrombocytopenia, to a platelet count above 50,000/µL. In these trials, fedratinib achieved significant spleen volume reduction in ~30-45% of patients and improvement in total symptom scores in 35-40% with good tolerability.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.
View Article and Find Full Text PDFSignal Transduct Target Ther
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi, China.
The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.
View Article and Find Full Text PDFHematol Oncol
January 2025
Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
Anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma (ALCL) typically affects young individuals and, despite high responsiveness to cytotoxic drugs, relapses occur in over 50% of patients. Crizotinib has improved outcomes, but its management in patients desiring parenthood remains an issue. This study presents the first description of four successful pregnancies during crizotinib treatment for ALK+ALCL: a female patient achieving two pregnancies through assisted reproductive technologies (ART), temporarily discontinuing crizotinib and maintaining a complete remission (CR), and a male patient conceiving naturally while on continuous therapy.
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