Although less potent than the nanomolar-range reference drug Epothilone B (IC50 < 0.1 μM), rugulosin A showed submicromolar-to-low micromolar efficacy with notable selectivity toward cancer cells, which is considered significant for an unoptimized natural product scaffold. Its antiproliferative activity against K562 cells (GI50 = 3.69 μM), benchmarked against Imatinib (GI50 = 0.373 μM), also falls within the active range of natural product leads...Molecular docking revealed strong binding energies (-10.1, -9.8, and -11.0 kcal/mol), along with a stable molecular dynamics simulations data. These findings highlight rugulosin A (3) as a promising anticancer lead that modulates major apoptosis signaling pathways.
Given unresectability, the patient received toripalimab (240 mg) combined with docetaxel and cisplatin every 3 weeks. To our knowledge, this is the first reported case of toripalimab-based chemoimmunotherapy demonstrating an early partial response and short-term disease control in unresectable maxillary sinus NUT carcinoma. It supports the potential role of PD-1 blockade integrated with platinum-taxane chemotherapy as a component of multimodal management for sinonasal NUT carcinomas.
27 days ago
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • NUTM1 (NUT Midline Carcinoma Family Member 1)
His treatment was started with docetaxel, receiving five cycles with good tolerance, after which he received hormonal treatment. After the infusion of 11 mL, the patient presented pharyngeal obstruction with dyspnoea, facial erythema, genital pruritus, and cervical pain that required treatment with intramuscular epinephrine. The results of the allergy study were not concordant with clinical presentation and confirmed the poor predictive value of taxane skin tests.
NFE2L2 rs35652124C > T was identified as an independent predictive genetic factor for Grade 4 neutropenia in esophageal cancer patients treated with DCF chemotherapy.
By co-encapsulating COL and the chemotherapeutic agent docetaxel (DTX) into bovine serum albumin (BSA) nanoparticles, an "enzyme-enhanced penetration" strategy combined with chemo-immunotherapy synergy was achieved...The COL-mediated penetration strategy enables low-dose DTX to effectively induce ICD in deep tumor regions, resulting in a synergistic effect between chemotherapy and immunotherapy. This work provides a new reference for collagenase-based drug delivery strategies targeting deep tumors and expands the application prospects of low-dose chemotherapy-induced ICD in nanomedicine.
1 month ago
Journal
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HMGB1 (High Mobility Group Box 1) • CALR (Calreticulin)
Inhibition of cFLIP in combination with either TRAIL or docetaxel has the potential to be used as a novel therapeutic approach to provide more potent, long-lasting benefits to men with prostate cancer.
Mice were randomized to receive vehicle, docetaxel, or KLS-3021, administered on day 9 (prostate-confined) or day 29 (visible/locally invasive) after implantation of luciferase-labeled PC-3 cells. Mechanistic analyses revealed extracellular matrix degradation, enhanced viral spread, increased immune cell infiltration, M1 macrophage polarization, and features of immunogenic cell death in KLS-3021-treated tumors. These results collectively demonstrate the translational potential of KLS-3021 as a minimally invasive or neoadjuvant therapeutic strategy for prostate cancer, especially in patients for whom early, localized intervention is medically feasible.