sunitinib / Generic mfg. - LARVOL DELTA

Tolerability and Treatment Duration of Recommended vs Reduced Starting Doses of Vascular Endothelial Growth Factor (VEGF) Tyrosine Kinase Inhibitors (TKI) in Patients with Renal Cell Carcinoma (RCC) (HOPA 2026) - "Eligible patients include adults (≥18 years) with metastatic ccRCC who initiated therapy with cabozantinib, lenvatinib, or axitinib between January 1, 2017, and December 31, 2024...Exclusion criteria include patients participating in a clinical trial, receiving of sunitinib, pazopanib, or Cometriq formulations, and filling at outside pharmacies or through patient assistance programs... Results Pending"

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

KRDQN: An Interpretable Prediction Framework for Adverse Drug Reactions via Knowledge-Graph Reinforced Deep Q-Learning. (PubMed, Pharmaceuticals (Basel)) - "Furthermore, to demonstrate the practical value of the KRDQN prediction framework, we applied it to predict potential ADRs and their mechanism pathways for the drugs sunitinib and indomethacin. The results indicated that the KRDQN framework could identify biological mechanism pathways consistent with clinical evidence. In this study, we developed the reinforcement learning-based KRDQN predictive framework, which outperforms existing baselines in predictive performance and yields interpretable adverse drug reaction (ADR) predictions, thereby serving as a powerful tool for pharmacovigilance and clinical decision-making."

Adverse drug reaction • Journal

Clinical benefit of the HIF-2α inhibitor casdatifan (Cas) across molecular subtypes in clear cell renal cell carcinoma (ccRCC) patients from the ARC-20 Clinical Study (AACR 2026) - P1 | "The HIF-2α inhibitor Cas produces similar clinical benefit in all previously described molecular subtypes of ccRCC. While most ARC-20 patients derived benefit from Cas monotherapy, there was a strong relationship between clinical benefit (PFS) and expression levels of HIF-2α transcriptional signatures in tumor samples."

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1

Phospho-reprogramming mitochondrial respiration underlies sunitinib resistance in renal cell carcinoma (AACR 2026) - "MTT assay was additionally used to measure proliferation of naïve and TKI-resistant normal kidney and ccRCC cell lines upon TRAP1 inhibition with Gamitrinib-TPP...Furthermore, we observed that sunitinib-resistant ccRCC cell lines demonstrated increased sensitivity to TRAP1 inhibition. Collectively, our work demonstrates the potential for novel combination therapies for targeting TKI-resistant ccRCC."

IO biomarker • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • SDHA

In vitro profiling of IDRX-42 and NB003 against secondary and tertiary (AP/AL) mutations found in TKI-resistant GIST (AACR 2026) - "Approximately 70-75% of Gastrointestinal stromal tumor (GIST) harbor a KIT mutation and patients with KIT-mutant GIST have durable responses to front-line imatinib (IM)...For example, sunitinib (SU) is potent against AP mutations (V654A, T670I), but has minimal activity against AL mutations. Conversely, ripretinib (RIP) has minimal activity against AP mutations...Ideally, future development of these newer agents should focus on earlier lines of therapy, prior to the development of AP+ AL mutations. The pan-resistance of AP/AL mutations to existing TKIs indicates the need to develop new drugs to target these resistance mutations."

Preclinical • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

EZH2-AR non-canonical axis activation in TKI-resistant RCC: Differential effects of lenvatinib and cabozantinib (AACR 2026) - "Consistently, AR expression is observed in RCC lines resistant to sunitinib, dovitinib, and lenvatinib, but not with cabozantinib treatment...Overall, our findings suggest that EZH2-dependent kinase reprogramming drives AR phosphorylation and activation, contributing to drug resistance to selective TKIs. Cabozantinibunique ability to bypass AR/EZH2 upregulation underscores the need to explore alternative resistance pathways."

Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AR • EZH2

New Derivatives of 4-Piperidinylphenyl-Linked Thiazoles as VEGFR2 Inhibitors with Potential Cytotoxicity Against Renal Cancer. (PubMed, Biomolecules) - "Compounds 7c (IC50 = 0.073 ± 0.002 µM), 9b (IC50 = 0.049 ± 0.002 µM), and 9c (IC50 = 0.093 ± 0.003 µM) were the most potent, showing VEGFR2 inhibition superior to that of sunitinib (IC50 = 0.118 ± 0.003 µM)...The treatment of A498 renal cancer cells with compound 7c led to an apparent cell cycle arrest and a significant induction of apoptosis. A docking study was also conducted and revealed a proper orientation of compound 7c into the active site of VEGFR2."

Journal • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity. (PubMed, Metabolites) - "Metabolomic analyses of various TKIs identified convergent signatures along three interconnected axes: (1) mitochondrial bioenergetic dysfunction characterized by impaired long-chain fatty acid oxidation and adenylate depletion; (2) disruption of endothelial nitric oxide signaling with redox imbalance, including increased nitrotyrosine, Nox activation, and eNOS uncoupling; and (3) an inflammatory metabolic profile marked by elevated branched-chain and aromatic amino acids, creatine, and osmolytes. Rodent models of sunitinib and sorafenib replicate these signatures and demonstrate histological injury, contractile dysfunction, and fibrosis. Preclinical intervention data, particularly restoration of myocardial carnitine, AMPK signaling, and fatty acid oxidation by L-carnitine, provide proof of concept for metabolomics-guided cardioprotection. Metabolomics can identify mechanistic biomarkers that facilitate the early detection, risk stratification, and targeted prevention of..."

Journal • Review • Cardiovascular • Fibrosis • Immunology • Oncology • NOS3

Unveiling clear cell renal cell carcinoma heterogeneity associated with locally advanced disease using single nucleus multi-omics (AACR 2026) - "In contrast, while FOS-ccRCC signature also appears to be associated with disease recurrence, these cells are highly sensitive to various TKI and Sunitinib in particular. These results suggest the potential to leverage the differential therapeutic vulnerability of ccRCC subpopulations to provide better combination therapies in the clinic.With the goal of improving the conceptual framework for the design of adjuvant therapies, our study offers an in-depth characterization of ccRCC subpopulations that are associated with higher stages and disease progression, possibly through different druggable oncogenic pathways."

Heterogeneity • IO biomarker • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EDIL3

Non-animal platforms using ex-vivo human tissue and live-cell biosensors enable functional drug testing in renal cell carcinoma (AACR 2026) - "Treatment groups included: a) cabozantinib (cabo) alone, b) cabo with cemiplimab (cemi, a PD-1 inhibitor), c) cemi with fianlimab (fin, a LAG-3 inhibitor)...Cells were plated on biosensor-compatible microplates and treated with metabolic inhibitors (2-DG, oligomycin) and pharmacological targeted drugs relevant to RCC [(PI103- PI3K/mTOR inhibitor), sunitinib and cabozantinib (tyrosine kinase inhibitors), and linsitinib (IGF1R inhibitor)]... This integrated, fully non-animal strategy overcomes key limitations of animal models by combining preserved human tumor microenvironments with high-resolution metabolic biosensing. Together, these platforms enable rapid and mechanism-based profiling of therapeutic vulnerabilities in RCC."

Preclinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AMPK • HIF1A • LAG3

A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours (clinicaltrials.gov) - P2 | N=137 | Active, not recruiting | Sponsor: Canadian Cancer Trials Group | Trial completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Adrenal Cortex Carcinoma • Hepatocellular Cancer • Oncology • Ovarian Cancer • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • NF1 • PTEN • STK11

Effects of dentin extract without demineralization on migration and angiogenic potential of human umbilical vein endothelial cells. (PubMed, Biomed Mater Eng) - "In conclusion, this study demonstrates that DE, without demineralization, promotes cell proliferation, migration, and angiogenesis in HUVECs via the Notch and VEGF/VEGFR2 signaling pathways. These findings suggest that dentin, without the need for demineralization, could serve as a viable alternative to conventional bone graft materials, offering a more streamlined process for regenerative surgery."

Journal • TGFB1

In vivo discovery of blood-brain barrier opening small molecules with FishNAP. (PubMed, bioRxiv) - "Finally, testing three representative molecules (Calcitriol, Lovastatin, and Sunitinib) in adult mice revealed increased BBB permeability and reduced Claudin-5 expression, demonstrating conserved mechanisms of BBB-regulation across vertebrates. FishNAP thus enables systematic discovery of BBB modulators with direct translational potential for brain drug delivery."

Journal • Preclinical • CNS Disorders • CLDN5

Identification and Validation of RORC as a Circadian Rhythm-Related Biomarker in Gastric Cancer. (PubMed, Int J Gen Med) - "Drug sensitivity analysis indicates that the RORC gene is responsive to agents such as VX-680, MG-132, and Sunitinib. Cell biology experiments have confirmed that RORC overexpression significantly diminishes the proliferation, invasion, and migration capabilities of gastric cancer cells. Integrating bioinformatics and cell biology experiments suggests that RORC, a gene associated with rhythm regulation, acts as a tumor suppressor gene that is underexpressed in gastric cancer, thereby serving as a potential biomarker and therapeutic target for this malignancy."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • ARID1A • RORC • TP53

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P4 ➔ P3

Phase classification • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P4 trial • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2028 ➔ Jul 2028 | Trial primary completion date: Dec 2028 ➔ Jul 2028

Trial completion date • Trial primary completion date • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

Validation of a 15-Gene Prognostic Signature in Metastatic Clear Cell Renal Cell Carcinoma. (PubMed, JCO Precis Oncol) - "The 15G score was independently prognostic in metastatic ccRCC among patients receiving different systemic therapy regimens."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Phase Ib/II Trial of Envafolimab Plus Lenvatinib for Subjects With Solid Tumors (clinicaltrials.gov) - P1/2 | N=170 | Recruiting | Sponsor: 3D Medicines (Sichuan) Co., Ltd. | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Carcinoma

GLOMERULAR ENDOTHELIAL CELL-DERIVED ET-1 PROMOTES PODOCYTE INJURY VIA ETAR/PKM2 SIGNALING IN SUNITINIB-ASSOCIATED NEPHROTOXICITY (ISN-WCN 2026) - "Therapeutic experiments evaluated Atrasentan (ETAR antagonist) and Shikonin (PKM2 inhibitor) for 4 weeks, with renal pathology assessed by PAS staining and electron microscopy.Results Serum analysis of 31 mRCC patients showed significant circulating ET-1 elevation following sunitinib therapy, with higher levels observed in those with severe proteinuria. Mechanistically, GEC-derived ET-1 activated ETAR/β-arrestin-1 signaling in adjacent podocytes, promoting PKM2 dimerization and nuclear translocation, which in turn activated NF-κB signaling and oxidative stress. Pharmacological blockade of ETAR or inhibition of PKM2 attenuated podocyte injury and reduced proteinuria.Conclusion GEC-derived ET-1 promotes podocyte injury via ETAR/PKM2 signaling in sunitinib-induced nephrotoxicity.Targeting ET-1/ETAR signaling and PKM2-mediated glycolytic reprogramming may represent novel therapeutic strategies to mitigate sunitinib-associated nephrotoxicity, with potential implications for..."

Genito-urinary Cancer • Nephrology • Renal Cell Carcinoma • Solid Tumor • EDN1 • PKM

DR5/WDR12 balances p65 stability promoting sunitinib resistance in renal cell carcinoma. (PubMed, Cell Death Differ) - "Clinically, ccRCC patients with high DR5 expression show decreased responsiveness to TKI-based therapy. Collectively, these results highlight the importance of the positive feedback loop involving the DR5/NF-κB axis in sunitinib resistance and provide an effective therapeutic strategy for overcoming resistance."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Targeted Protein Degradation • BCL2 • CUL4B • DDB1 • TNFRSF10B

Short and Long Non-Coding RNAs in Renal Cell Carcinoma. (PubMed, Noncoding RNA) - "Moreover, the manuscript discusses ncRNA-mediated mechanisms of resistance to targeted therapies such as sunitinib, sorafenib, and axitinib, emphasizing regulatory networks involving miRNA targets, lncRNA-miRNA sponging, RNA-binding proteins, extracellular vesicle transfer, and epigenetic modulation. Emerging therapeutic opportunities are also addressed, including strategies aimed at inhibiting oncogenic ncRNAs or restoring tumor-suppressive ncRNAs to enhance drug sensitivity and improve patient stratification."

Journal • Review • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Efficacy and safety of nivolumab monotherapy in patients with unresectable clear cell sarcoma and alveolar soft part sarcoma (OSCAR Trial/NCCH1510). (PubMed, Cancer) - "The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS."

Journal • Monotherapy • Alveolar Soft Tissue Sarcoma • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • TFE3