Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis, and new therapies are a major clinical need. When mutated, FLT3 drives neoplastic cell proliferation. New drugs (i.e., tyrosine kinase inhibitors, TKIs) showed effectiveness in FLT3-AML and promise to change disease history and outcome. We evaluated the benefit conferred by TKIs in terms of survival, burden of complications and surrogate endpoint of quality of life in a retrospective cohort of 49 FLT3 positive, R/R AML patients. Patients who received TKIs were compared to those treated with conventional chemotherapy. Treatment with TKIs conferred a better OS and wea associated with a lower burden and severity of adverse events. Importantly, patients who received TKIs showed reduced time of hospitalization. In conclusion, treatment with TKI in R/R FLT3-AML was related to a better survival, less and milder AEs, and shorter hospitalization.
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http://dx.doi.org/10.1016/j.leukres.2020.106497 | DOI Listing |
Eur Thyroid J
January 2025
D Salvatore, Department of Public Health, University of Naples Federico II, Naples, Italy.
Objective: To analyse at our Institution the criteria for selecting a first-line therapy for patients with an advanced radioiodine-refractory thyroid cancer, their clinical responses, safety and survival outcomes.
Patients And Methods: We extracted data from 69 consecutive patients referred from September 2016 to September 2024 at Federico II University Hospital, among whom 44 patients were treated with TKIs as first line treatment and outside any clinical trial, and form the basis of this report.
Results: Thirty-one (71%) patients were treated with the antiangiogenesis inhibitor lenvatinib and 13 (29%) with selective tyrosine kinase inhibitors (s-TKIs).
J Exp Med
March 2025
Institute of Cancer Research, Shenzhen Bay Laboratory , Shenzhen, China.
BRAF mutations drive initiation and progression of various tumors. While BRAF inhibitors are effective in BRAF-mutant melanoma patients, intrinsic or acquired resistance to these therapies is common. Here, we identify non-receptor-type protein tyrosine phosphatase 23 (PTPN23) as an alternative effective target in BRAF-mutant cancer cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037-1002.
Nutritional status is a determining factor for growth during development and homeostatic maintenance in adulthood. In the context of muscle, growth hormone (GH) coordinates growth with nutritional status; however, the detailed mechanisms remain to be fully elucidated. Here, we show that the transcriptional repressor B cell lymphoma 6 (BCL6) maintains muscle mass by sustaining GH action.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry and Chemical Biology, TU Dortmund University and Drug Discovery Hub Dortmund (DDHD), Zentrum für Integrierte Wirkstoffforschung (ZIW), Otto-Hahn-Strasse 4a, Dortmund 44227, Germany.
Gastrointestinal stromal tumors (GIST), driven by KIT and PDGFRA mutations, are the most common mesenchymal tumors of the gastrointestinal tract. Although tyrosine kinase inhibitors (TKIs) have advanced treatment, resistance mutations and off-target toxicity limit their efficacy. This study develops covalent TKIs targeting drug-resistant GIST through structure-based design, synthesis, and biological evaluation.
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