Publications by authors named "Jumana Afaghani"
Article Synopsis
- SF3B1 mutations are common in cancer but lack directed treatments. Recent trials of XPO1 inhibitors in high-risk myelodysplastic neoplasms (MDS) found that patients with these mutations respond better to treatment.
- The study explores how these mutations affect RNA behavior when XPO1 is inhibited, leading to altered splicing and activation of apoptotic pathways in the mutant cells.
- Researchers identified that combining eltanexor (an XPO1 inhibitor) with venetoclax (a BCL2 inhibitor) effectively targets SF3B1 mutant cells while minimizing toxicity, paving the way for new treatment strategies for high-risk MDS.
STK17A is a novel uncharacterized member of the death-associated protein family of serine and threonine kinases. Overexpression of STK17A is observed in many cancers. We identified a lead compound that is based on a quinazoline core.
View Article and Find Full Text PDFXPO1 (Exportin-1) is the nuclear export protein responsible for the normal shuttling of several proteins and RNA species between the nucleocytoplasmic compartment of eukaryotic cells. XPO1 recognizes the nuclear export signal (NES) of its cargo proteins to facilitate its export. Alterations of nuclear export have been shown to play a role in oncogenesis in several types of solid tumour and haematologic cancers.
View Article and Find Full Text PDFPatients with multiple myeloma-bearing translocation t(11;14) have recently been shown to benefit from the apoptosis-inducing drug venetoclax; however, the drug lacks FDA approval in multiple myeloma thus far due to a potential safety signal in the overall patient population. Selinexor is an inhibitor of nuclear export that is FDA-approved for patients with multiple myeloma refractory to multiple lines of therapy. Here, we report that in four patients with multiple myeloma with t(11;14), the concomitant administration of venetoclax and selinexor was safe and associated with disease response.
View Article and Find Full Text PDFArticle Synopsis
- Covalent Bruton's tyrosine kinase (BTK) inhibitors have significantly improved treatment for B-cell cancers, such as chronic lymphocytic leukemia (CLL), but patients can develop resistance due to mutations at the BTK binding site and other mechanisms.
- This study analyzed genomic data from CLL patients treated with the noncovalent BTK inhibitor pirtobrutinib and identified several mutations in BTK and phospholipase C gamma 2 (PLCγ2) that contribute to resistance.
- The findings highlight new mechanisms of resistance that allow CLL to escape treatment effects, affecting both noncovalent and certain covalent BTK inhibitors, indicating a need for further research in overcoming these challenges.
A Moving Target: Inactivating BTK Mutations as Drivers of Follicular Lymphoma.
Clin Cancer Res
April 2021
Drugs that target Bruton tyrosine kinase (BTK) have been highly successful and changed the landscape of therapies in B-cell lymphomas. However, their lower rates of effectiveness in follicular lymphoma are unexplained. Recent work describes inactivating BTK mutations that show that at least some follicular lymphomas do not require BTK.
View Article and Find Full Text PDFPurpose: The kidney is a radiosensitive late-responding normal tissue. Injury is characterized by radiation nephropathy and decline of glomerular filtration rate (GFR). The current study aimed to compare two rapid and cost-effective methodologies of assessing GFR against more conventional biomarker measurements.
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