Votrient (pazopanib)

Consistently, knockdown of Nrf2 restored the expression of p53 and PAI in ACHN cells. Based on these results, we explored a novel mechanism whereby which Pazopanib displays a cytotoxicity effect in RCC cells through promoting cellular senescence mediated by Nrf2.

Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.

When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting programed cell death protein 1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.

P1/2, N=59, Recruiting, University Hospital, Bordeaux | Not yet recruiting --> Recruiting

P1/2, N=58, Recruiting, Centre Leon Berard | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P3, N=129, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2027 --> Feb 2025

P2, N=32, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024

P1, N=54, Active, not recruiting, National Cancer Institute (NCI)

Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.

P1, N=20, Not yet recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Combined use of PZP and CRZ offers synergic anti-tumor effects against OS, inducing apoptosis in vitro and in vivo by down-regulating AKT and STAT3. Our data suggest that these agents can be used for patients clinically.

We have developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug that targets both VEGFR1 and VEGFR2 (Nano-PAZII)...Simultaneously, the inhibition of VEGFR2 reduces cartilage degeneration. These findings provide a mechanism-based disease-modifying drug strategy that addresses both pain symptoms and cartilage loss in OA.

P3, N=333, Not yet recruiting, Intensity Therapeutics, Inc.

P2/3, N=140, Active, not recruiting, National Cancer Institute (NCI)

P1/2, N=51, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=900, Recruiting, Centre Leon Berard | N=560 --> 900 | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

P1/2, N=139, Recruiting, St. Jude Children's Research Hospital | Not yet recruiting --> Recruiting

Thus, we focused on representative TKIs associated with severe hepatic adverse events, namely lapatinib, pazopanib, regorafenib, and sunitinib as objections of study, then integrated drug side-effect data from United State Food and Drug Administration (U.S. Based on the target prediction results of drugs and reactive metabolites, we also shed light on the association between toxic metabolites and severe hepatic adverse reactions, and thinking HSPA8, HSPA1A, CYP1A1, CYP1A2 and CYP3A4 were potential therapeutic or preventive targets against TKI-induced liver injury. In conclusion, our research provides comprehensive insights into the mechanism underlying severe liver injury caused by TKIs, offering a better understanding of how to enhance patient safety and treatment efficacy.

This study analyzed the extensive regulatory mechanisms of m6A modification on oxidative stress, the tumor microenvironment, and immunity. Quantifying m6A scores may enhance immunotherapeutic effects and assist in developing more effective agents.

P1/2, N=139, Not yet recruiting, St. Jude Children's Research Hospital

Drug sensitivity analysis revealed that OS patients with a low Tex risk were responsive to Dasatinib and Pazopanib. Finally, immunohistochemistry verified that MYC and FCGR2B were significantly upregulated in OS tissues compared with adjacent tissues. This study investigates the role of Tex within the TIME of OS, and offers novel insights into the mechanisms underlying disease progression as well as the potential treatment strategies for OS.

The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.

PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.

CD20 B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

P1, N=350, Active, not recruiting, Eli Lilly and Company | Trial completion date: Nov 2023 --> Aug 2024

P3, N=413, Recruiting, Xynomic Pharmaceuticals, Inc. | Trial completion date: Jun 2023 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Dec 2024

P1, N=90, Active, not recruiting, Pamela Munster | Recruiting --> Active, not recruiting

P2, N=180, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC.

Lower IC50 values of imatinib, pazopanib, and sorafenib in the high-CuRA group revealed the potential value of these drugs. Knockdown of SFT2D1 significantly inhibited ability of the proliferation, migration, and invasive in cervical cancer cells. CuRA gene signature provided valuable insights into the prediction of prognosis and immune microenvironment of cervical cancer, which could help develop new strategies for individualized precision therapy for cervical cancer patients.

Besides, compared to the low-risk group, there were higher expressions of most immune checkpoint genes and HLA genes in the high-risk group, and the high-risk patients showed higher sensitivity to the chemotherapy and targeted drugs (axitinib, dasatinib, pazopanib, saracatinib, sunitinib and temsirolimus). The novel CRG signature may act as a reliable, efficient tool for prognostic prediction and treatment guidance in future clinical practice.

Senescence genes were related to the prognosis, response to chemotherapy drugs, and TME of GC. Our senescence-related risk model could forecast the survival of patients, their response to chemotherapy drugs, and the TME to a certain extent.

P2/3, N=190, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | N=70 --> 190

Of the drugs used in second-line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L-sarcoma), eribulin for liposarcoma, and pazopanib for non-liposarcoma. The present study demonstrated the potential of tailored therapy guided by mutation profiles established by comprehensive genomic profiling testing in optimizing second-line chemotherapy for STS. The findings of this study will hopefully contribute some valuable insights into enhancing STS treatment strategies and outcomes.

Patients with high expression of TMEM178 have better prognosis and are more sensitive to targeted drug Pazopanib. Immune infiltration analysis showed that the infiltration levels of CD4 T cell subsets were reduced in BRAC tissues with high TMEM178 expression, and immunosuppressive molecules of T-cell exhaustion were lower expression level. Hypermethylation of the TMEM178 promoter region was a contributing factor to the downregulation of its expression, and TMEM178 may reflect a prognostic and immunosuppressive situation in BRCA.

Angio TRS was then validated in a separate cohort of 86 patients with RCC treated with single agent systemic VEGFR TKI (median follow-up 29.2 months; 76% male, 77% clear cell, 14% with sarcomatoid features, 84% 1st line, and 71% treated with sunitinib, pazopanib or axitinib); 52% of patients were Angio TRS High. Angio TRS is a multivariate expression-based algorithm performed on FFPE tumor tissue, validated to be prognostic of clinical outcome for patients with RCC treated with single agent VEGFR TKI when controlling for clinical factors. Angio TRS may support individualized treatment decision making in patients with advanced RCC. Additional independent validation in a cohort of Kaiser Permanente patients will be presented.

Retrospective analyses were conducted using two cohorts: 533 tumors from the Cancer Genome Atlas Project (TCGA) with emphasis on early-stage disease and 409 archival tumors collected from patients receiving pazopanib or sunitinib on the phase 3 COMPARZ trial in metastatic RCC. HIF-2α target activation was adversely associated with survival in early and late stage ccRCC while angiogenesis scores correlated favorably. HIF-2α targets other than VEGF appear to have clinical impact and should be explored. HIF-2α-SIG may prove helpful for clinical development of targeted HIF-2α inhibitors and deserves further study.

P1/2, N=51, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting

P4, N=30, Not yet recruiting, University Medical Center Groningen | Initiation date: Sep 2023 --> May 2024

Multi tyrosine kinase inhibitors (mTKIs) cabozantinib and vandetanib are good first line options, even vandetanib prescription is currently limited to RET mutated patients. Selective RET inhibitors such as pralsetinib could be a preferred upfront treatment in case of RET mutated MTC presenting common or gatekeeper RET mutations (e.g. M918T; V804L/M). Selpercatinib, otherwise, can be prescribed as the second line after disease progression to mTKIs. The best option for subsequent lines is to consider inclusion in clinical trials or alternatively other mTKIs such as sunitinib, sorafenib, lenvatinib, or pazopanib could be evaluated. New perspectives include next-generation RET inhibitors able to overcome resistance mechanisms responsible for disease progression to standard mTKIs and RET inhibitors, and immunotherapy for MTC presenting with high tumor mutational burden.

Other reported targeted therapies for malignant GCTs included pazopanib in combination with crizotinib, which showed disease control for four months in one patient, and a PI3K inhibitor which achieved disease control for nine months in another patient. Dasatinib and megestrol were ineffective in two other different patients. Pazopanib has been demonstrated to be active in advanced GCTs and may be considered as a preferable treatment option.

P2, N=171, Active, not recruiting, National Cancer Institute (NCI)