Notably, the UBE2O crosslinking inhibitor arsenic trioxide (ATO) reduced PD-L1 expression and enhanced the efficacy of radioimmunotherapy in preclinical lung cancer models while exhibiting acceptable short-term tolerability. Our findings indicate that targeting the UBE2O/CDKL1 axis may represent a highly promising strategy for increasing lung cancer sensitization to radioimmunotherapy.
1 day ago
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • YBX1 (Y-Box Binding Protein 1) • CDK1 (Cyclin-dependent kinase 1)
We identified polyprenoic acid (PA, peretinoin) as the first ligand capable of directly binding HNF4A...Importantly, hepatocyte-specific Hnf4a knockdown or lipid-nanoparticle-mediated Hnf4a siRNA abrogated the protective effects of PA. These findings establish HNF4A as a pharmacologically controllable tumor suppressor and highlight PA-like compounds as promising agents for preventing liver carcinogenesis.
5 days ago
Journal
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AFP (Alpha-fetoprotein) • SLCO1B3 (Solute carrier organic anion transporter family member 1B3) • HNF1A (HNF1 Homeobox A) • PDGFC (Platelet Derived Growth Factor C)
Histopathological analysis showed that the combination group had less cell proliferation (as evidenced by reduced Ki-67 expression) and greater tumor necrosis. This study reveals the synergistic effects of Oncomed and ATO, suggesting a potential combinatorial strategy to address the limitations of current cancer treatments and improve patient outcomes.
P2, N=9, Active, not recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Mar 2025 --> Dec 2026
8 days ago
Enrollment closed • Trial completion date • Trial primary completion date
Acute promyelocytic leukemia (APL) is a highly curable form of acute myeloid leukemia (AML) when treated early with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)...The ATRA-ATO regimen showed substantial remission rates, but early deaths remain a concern. Increased survival rates in resource-constrained environments require improved early detection, referral, and supportive care.
Suspicion for DS should be heightened in patients with acute promyelocytic leukemia (M3 AML) who recently started induction chemotherapy, including all-trans retinoic acid or arsenic trioxide, and in those with non-M3 AML receiving differentiation agents (i.e., isocitrate dehydrogenase inhibitors, menin inhibitors, FMS-like tyrosine kinase 3 inhibitors)... DS represents a diagnostic challenge in the ED due to its nonspecific presentation and mimicry of infection. A high index of suspicion, combined with targeted imaging, laboratory evaluation, and early corticosteroid therapy, can improve outcomes.
c-Myc activation is a key driver of VEN resistance in t(8;21) AML. HHT acts as a mechanistically complementary agent, restoring VEN sensitivity. These results provide a preclinical rationale for clinical evaluation of VEN-HHT combination therapy in genetically defined AML subsets.