pazopanib

ISR activation and RIPK3-mediated necroptosis converge to drive epithelial injury and barrier dysfunction in CD. Repurposing pazopanib and ponatinib offers a potentially translatable approach to restore barrier integrity in CD.

Importantly, melatonin works with TKIs like sunitinib and pazopanib to improve mitochondrial homeostasis and increase therapeutic effectiveness. Overall, melatonin provides a multi-targeted, low-toxicity strategy for overcoming metabolic and therapeutic resistance in RCC, emphasizing its translational promise as an adjuvant. Further clinical trials should concentrate on dose optimization, biomarker-guided patient selection, and combination regimens that include immune checkpoint blockade.

Recent clinical trials (Axi-STS, TAPPAS) demonstrated that single-agent anti-angiogenic inhibitors (axitinib, pazopanib) achieve modest efficacy (median progression-free survival (PFS) 3.0-4.3 months, response rates 5-13%), underscoring angiosarcoma's complex, multipathway-driven pathogenesis. Environmental exposures (vinyl chloride, thorotrast, radiation) drive distinct angiosarcoma subtypes with subtype-specific mutational profiles. We propose that precision-medicine approaches integrating molecular stratification, pathway crosstalk analysis, and biomarker-guided combination therapies represent the rational next steps to overcome therapeutic resistance and improve clinical outcomes in this lethal malignancy.

P2, N=216, Completed, Melanoma Institute Australia | Trial completion date: Dec 2025 --> Mar 2026

Mice were randomized into vehicle control or four sequential treatment groups (Everolimus→Sunitinib [E→S], Sunitinib→Everolimus [S→E], Pazopanib→Sunitinib [P→S], Pazopanib→Everolimus [P→E]). This RCC PDOX platform faithfully preserves patient-specific biology-including metastatic propensity, engraftment efficiency, growth kinetics, and stromal dependency-while enabling real-time evaluation of sequential targeted therapies. Given the limited number of models tested, these findings provide proof-of-concept for individualized treatment exploration in advanced RCC and support future investigation of rational combinations with immune checkpoint blockade in humanized or immunocompetent systems.

Importantly, pharmacological inhibition of HNRNPU K181 lactylation by Pazopanib suppresses PHGDH expression and tumor growth, underscoring its translational potential. Collectively, our findings uncover a lactate-driven regulatory axis in which HNRNPU K181 lactylation integrates metabolic signaling with post-transcriptional regulation to promote cervical cancer progression, providing a promising therapeutic avenue for targeting metabolic vulnerabilities in malignancies.

The patient initially received one cycle of adriamycin-ifosfamide-mesna (AIM), which was discontinued due to toxicity, followed by five cycles of vincristine-doxorubicin-cyclophosphamide (VDC), resulting in a near-complete metabolic response. Serial fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging confirmed a sustained complete metabolic remission beyond 18 months with minimal toxicity. This case highlights the marked chemosensitivity of BCOR-altered URCS to anthracycline-vinca-based chemotherapy and suggests a potential role for vascular endothelial growth factor (VEGF)-directed maintenance therapy in sustaining remission.

P1/2, N=51, Active, not recruiting, Centre Antoine Lacassagne | Recruiting --> Active, not recruiting

Despite subtotal resection and pazopanib therapy, the disease progressed and the patient died at 14 years of age. This case highlights persistent functional morbidity and later malignant progression during the long-term course of NF1-associated pelvic disease.

The findings demonstrated that nicardipine significantly inhibited the metabolism of pazopanib both in vitro and in vivo, leading to substantially increased systemic exposure of pazopanib. This clinically significant finding suggests that, when these two drugs are used in combination, plasma drug concentrations should be closely monitored and the need for dose adjustment should be considered.

The regimen was ineffective in bevacizumab-naïve patients and only narrowly met its predetermined endpoint in patients with prior BEV. These results do not support the combination regimen as tested in this protocol for further investigation in GBM.

Molecular profiling leveraged IMmotion151 (A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma) trial data with whole-exome sequencing, RNA sequencing, and programmed cell death ligand 1 immunohistochemistry. Systemic standard of care treatments for mRCC, which include vascular endothelial growth factor receptor targeted therapy (VEGF-TT [sunitinib or pazopanib]), immune-oncology-VEGF (IO-VE [pembrolizumab and axitinib, pembrolizumab and lenvatinib, nivolumab and cabozantinib, or avelumab and axitinib]), and 2 IO (IO-IO [ipilimumab and nivolumab]) regimens...In this cohort study, the very favorable risk subgroup had a less immunogenic molecular profile and superior outcomes from VEGF-containing regimens (VEGF-TT and IO-VE) compared with the favorable risk group. The IO-IO combination showed significantly worse survival in this population, suggesting that VEGF inhibition remains essential for optimal outcomes.