Publications by authors named "S Shacham"
Article Synopsis
- The nuclear export receptor XPO1 is commonly overexpressed in cancer cells, leading to mislocalization of important proteins; the inhibitor selinexor reverses this effect by blocking XPO1-cargo binding.
- Selinexor triggers the degradation of XPO1 through a specific mechanism involving the cullin-RING E3 ubiquitin ligase (CRL) system and its substrate receptor ASB8.
- Research using cryogenic electron microscopy revealed that selinexor stabilizes XPO1 in a unique conformation, allowing ASB8 to bind effectively and facilitate ubiquitination, showcasing a new method of protein degradation that differs from previously known molecular glue strategies.
Purpose: Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC.
Patients And Methods: ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries.
Article Synopsis
- * Data from 11 heavily pretreated patients indicate that selinexor (X) regimens show strong effectiveness and produce lasting responses, even when used later in treatment.
- * X-containing regimens resulted in better overall response rates and longer progression-free survival compared to previous anti-BCMA treatments, highlighting their potential in addressing an ongoing treatment gap.
Chordoma is a rare cancer that grows in the base of the skull and along the mobile spine from remnants of embryonic notochord tissue. The cornerstone of current treatments is surgical excision with adjuvant radiation therapy, although complete surgical removal is not always possible. Chordomas have high rates of metastasis and recurrence, with no approved targeted agents.
View Article and Find Full Text PDFNPM1 is the most frequently mutated gene in adults with acute myeloid leukemia (AML). The interaction between mutant NPM1 (NPM1c) and exportin-1 (XPO1) causes aberrant cytoplasmic dislocation of NPM1c and promotes the high expression of homeobox (HOX) genes, which is critical for maintaining the leukemic state of NPM1-mutated cells. Although there is a rationale for using XPO1 inhibitors in NPM1-mutated AML, selinexor administered once or twice per week did not translate into clinical benefit in patients with NPM1 mutations.
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