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S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.
Int J Biol Sci
January 2025
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.
View Article and Find Full Text PDFONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress.
J Exp Clin Cancer Res
January 2025
Cancer Biology Graduate Program, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Background: Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction.
View Article and Find Full Text PDFSevere hypophosphataemia following denosumab administration successfully managed using a calcimimetic agent.
BMJ Case Rep
January 2025
Pediatrics, Shiga University of Medical Science, Otsu, Shiga, Japan.
Denosumab, an anti-RANKL antibody, induces bone metabolism to a low-turnover bone status by arresting osteoclast activity. Frequent adverse events include infusion reactions, fever and hypocalcaemia but not hypophosphataemia. We report a case of severe hypophosphataemia associated with secondary hyperparathyroidism following denosumab administration in a young boy with recurrent osteosarcoma who was successfully treated with evocalcet.
View Article and Find Full Text PDFWilson's disease manifesting as refractory rickets.
BMJ Case Rep
January 2025
Neurology, King George's Medical University, Lucknow, Uttar Pradesh, India
Wilson's disease is a metabolic disorder affecting the liver, brain, skin and osteo-muscular organs. Refractory rickets is an unusual phenomenon in Wilson's disease. This 27-year-old man was primarily treated for rickets for 20 years without success and later developed features of tremulousness of limbs and dysphonia when he was evaluated for Wilson's disease.
View Article and Find Full Text PDFTemozolomide treatment in refractory pituitary adenomas and pituitary carcinomas.
Neuroendocrinology
January 2025
Background: Temozolomide (TMZ), a non-classical alkylating agent, possesses lipophilic properties that allow it to cross the blood-brain barrier, making it active within the central nervous system. Furthermore, the adverse reactions of the TMZ are relatively mild, which is why it is currently recommended as a first-line chemotherapy drug for refractory pituitary adenomas (RPAs) and pituitary carcinomas (PCs).
Summary: Systematic evaluations indicate a radiological response rate of 41% and a hormonal response rate of 53%, underscoring TMZ clinical efficacy, particularly when combined with radiotherapy.
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