Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Royalty - 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

Comparative Safety and Tolerability of Tyrosine Kinase Inhibitor and Immunotherapy Combination Therapies for Clear Cell Renal Cell Carcinoma: A Retrospective Review (HOPA 2026) - "This will be a retrospective chart review of patients between 18 and 89 years old diagnosed with ccRCC who initiated treatment with axitinib/pembrolizumab, lenvatinib/pembrolizumab, or cabozantinib/nivolumab at AHN between August 1, 2021 and August 31, 2025... Pending results and data analysis."

Combination therapy • Retrospective data • Review • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

303: NET Gains: Advances in Neuroendocrine Tumor Treatment (HOPA 2026) - "This session will review the data supporting these approvals and place them in the context of the broader treatment landscape for patients with endocrine malignancies. UAN: 0465-0000-26-062-L01-P Knowledge or Application Based: Application Learning Objectives: Understand the current treatment landscape for the spectrum of endocrine tumorsEvaluate the clinical trial data supporting the use of cabozantinib and belzutifan in the treatment of patients with various endocrine tumors"

Neuroendocrine Tumor • Oncology • Solid Tumor

Evaluating the unfolded protein response as a therapeutic target in clear cell renal cell carcinoma patients (AACR 2026) - "We observed decreased cell viability in PERK-silenced cells following cabozantinib (VEGF inhibitor) exposure, either through drug inhibition or genetic deletion. In summary, as clinical interest in PERK inhibition (PERKi) grows across multiple solid tumors, our findings highlight PERK as a potential therapeutic target in ccRCC and identify associated biomarkers that may inform future clinical strategies."

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

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

Combination of the GCN2 activator HC-7366 with VEGFR-TKI results in greater efficacy than VEGFR-TKI alone or VEGFR-TKI/HIF-2i combinations in ccRCC (AACR 2026) - P1 | "HC-7366 alone achieved 63% tumor growth inhibition (TGI), whereas cabozantinib alone induced 30% regression (1/8 PR) and lenvatinib alone produced 95% TGI...Furthermore, in a single mouse trial of 10 RCC PDX models, addition of HC-7366 to axitinib improved outcomes in 8/10 PDX models and was superior to the belzutifan/axitinib doublet in multiple models...A phase 1b clinical trial is now ongoing to evaluate the safety, tolerability, and efficacy of both HC-7366/belzutifan and HC-7366/cabozantinib doublets in metastatic ccRCC (NCT06234605). These results will form a foundation for future evaluation of triplet combinations that integrate HC-7366, VEGFR-TKIs, and HIF-2 inhibitors."

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EPAS1 • HIF1A

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

Evaluation of the circulating angiome in cancer: Translational assessment of a 44-plex angiogenesis biomarker panel (AACR 2026) - P1 | "Pharmacodynamic biomarker modulation was explored using retrospective plasma samples from two NCI studies —Cabozantinib + Panitumumab (NCT02008383) and Bevacizumab (NCT00416637)...This 44-plex panel demonstrates robust analytical performance, sensitivity, and reproducibility on the MSD® U-PLEX platform. The assay supports harmonized angiogenesis profiling, enabling standardized angiogenesis biomarker assessment in oncology research."

Biomarker • Oncology • IL6

Evolving toward precision oncology: Leveraging collateral drug responses for personalized second-line osteosarcoma treatment (AACR 2026) - "Objective: We aimed to model the evolution of chemoresistance to methotrexate, doxorubicin, and cisplatin (MAP) in vitro and to characterize collateral drug sensitivity and resistance patterns over time, potentially informing second-line treatment strategies in chemo resistant primary or recurrent disease. Five evolutionary replicates of MG63.3 osteosarcoma cells were treated with six complete cycles of pulsed, clinically relevant doses of cisplatin and doxorubicin, alternating with methotrexate...Collateral resistance emerged to etoposide, vincristine, and topotecan, while sensitivity increased to gemcitabine, cabozantinib, and palifosfamide... Our model reveals temporally dynamic, heterogeneous collateral responses during the development of chemoresistance to MAP in osteosarcoma. While cross-resistance to several agents emerged, collateral sensitivity to gemcitabine and cabozantinib supports a second line use for these agents. These data may inform rational sequencing..."

Clinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Novel inhibitors of BCRP and P-gp found among drugs used in the treatment of cancer (AACR 2026) - "Of the investigated compounds, cabozantinib (IC50 of 0.65 µM), midostaurin (0.69 µM), and entrectinib (5.8 µM) showed the strongest inhibition of BCRP. Nilotinib (1.0 µM), osimertinib (2.0 µM), and abemaciclib (2.4 µM) showed the strongest inhibition of the P-gp. The highest I2/IC50 ratios for BCRP were observed for mitotane (6190), cabozantinib (1730), and abiraterone (831). For P-gp, the highest I2/IC50 ratios were observed for nilotinib (2880), pazopanib (1580), and mitotane (1480)...The highest I1/IC50 ratios for BCRP were observed for doxorubicin (8.2), etoposide (2.8), and fosaprepitant (0.84). For P-gp, the highest I1/IC50 ratios were observed for amscarine (1.6), vinorelbine (0.55), and fosaprepitant (0.50)...Mechanistic static model for BCRP inhibitors suggested that cabozantinib, midostaurin, and apalutamide could almost fully inhibit intestinal BCRP, increasing the exposure to concomitantly administered rosuvastatin by 94%, 89%,..."

Breast Cancer • Oncology • Solid Tumor

Spatial proteomics reveals vasculature and immune modulation for overcoming doxorubicin resistance in breast cancer (AACR 2026) - "Leveraging this immune modulatory activity, we tested a systemic triple combination with anti-PD1 immunotherapy, which led to a significant and complete tumor regression. Our study demonstrates a rational drug combination that improves doxorubicin efficacy to overcome microenvironment-driven resistance for long-term breast cancer control."

Breast Cancer • Oncology • Solid Tumor

Targeting G6PD (Glucose-6-Phosphate Dehydrogenase) as a Biomarker of Therapeutic Vulnerability in Renal Cell Carcinoma. (PubMed, Int J Mol Sci) - "A high gene expression was observed in lenvatinib non-responder cell lines, and DepMap dose-response curves indicated modest responses to VEGF inhibitors. In vitro, ACHN was more sensitive to VEGF inhibition, particularly cabozantinib, whereas G6PDi-1 had stronger effects in 786-O, impairing viability, migration, and clonogenic capacity. Our findings support G6PD as a biomarker of tumor aggressiveness and G6PDi-1 as a potential therapeutic in RCC models."

Biomarker • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • G6PD • PRCC

Tyrosine Kinase Inhibitor Therapy in Metastatic Medullary Thyroid Carcinoma: Real-World Data from Turkish Oncology Group. (PubMed, J Clin Med) - "Background: Vandetanib and cabozantinib are the approved first-line antiangiogenic multikinase inhibitors (aaMKIs) for metastatic medullary thyroid carcinoma (MTC); however, real-world data on their comparative efficacy, optimal sequencing, and outcomes beyond the first-line setting remain limited...They are consistent with their central role in treatment sequencing, particularly in settings with limited access to selective RET inhibitors. Given the retrospective design and small subgroup sizes, these results should be interpreted as exploratory and hypothesis-generating."

Journal • Real-world evidence • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

CXCR4, CXCR7 and PBRM1 are responsible for everolimus and cabozantinib resistance in human renal cancer cells. (PubMed, Cell Death Discov) - "Interestingly, A498-RAD10 cells were cross-resistant to cabozantinib, the tyrosine kinase inhibitor used in first-line treatment of mRCC with nivolumab...In silico data supported a context‑dependent role of PBRM1 in ccRCC patients. To the best of our knowledge, this is the first description of a mechanism of RAD001 and cabozantinib resistance through PBRM1 overexpression and CXCR7/CXCR4 downregulation and suggest new therapeutic perspective for cabozantinib-resistant patients."

Journal • Clear Cell Renal Cell Carcinoma • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ACKR3 • CXCR4 • ERCC1 • PBRM1 • YY1

A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis (AACR 2026) - "Abstract is embargoed at this time."

Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Cabozantinib remodels the pancreatic tumor microenvironment to potentiate immunotherapy (AACR 2026) - "Abstract is embargoed at this time."

Biomarker • Late-breaking abstract • Tumor microenvironment • Oncology • Pancreatic Cancer • Solid Tumor

Preventing nk cell activation in the damaged liver induced by cabozantinib/pd-1 blockade increases survival in hepatocellular carcinoma models (AACR 2026) - "Surprisingly, systemic depletion of NK reduced hepatotoxicity elicited by the combination therapy without compromising its anti-cancer effect, and significantly enhanced the survival benefit even in mice with HCC and underlying liver fibrosis. These findings demonstrate that preventing NK activation allowed for maintaining a favorable therapeutic ratio when combining ICB with cabozantinib in advanced HCC models."

Hepatocellular Cancer • Oncology • Solid Tumor

From animals to computational oncology: Digital twins as ethical enablers of next-generation bone metastasis research (AACR 2026) - "We further conducted robust double verification by simulating both the anti-angiogenic effects of cabozantinib and the anti-resorptive effects of zoledronic acid...Computational compression tests revealed increased fragility in trabecular bone following treatment with the bone-targeting agent Radium-223, whereas three-point bending tests showed no fragility in cortical bone post-treatment...Overall, our digital twin approach provides a transformative platform to dissect tumor progression, predict therapy response, and evaluate the consequences on bone mechanics. By enabling these insights in silico, we aim to significantly reduce dependence on animal models, directly supporting and strengthening the 3Rs principle."

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

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

Two integrative molecular subtypes of hepatocellular carcinoma with predictive therapeutic potential: Toward liquid biopsy-guided precision medicine (AACR 2026) - "In the IMbrave150 cohort, the Immune subtype showed superior survival outcomes to atezolizumab-bevacizumab (p < 0.0001). Conversely, the METabolic subtype was associated with 100% recurrence after sorafenib treatment, suggesting potential benefit from MET inhibitors after sorafenib failure...Additionally, our study suggests the Immune subtype is an optimal candidate for immunotherapy combined with anti-VEGF(R) agents. Further validation in larger, prospective cohorts is warranted to translate these findings into clinical practice."

Biopsy • IO biomarker • Liquid biopsy • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • CTNNB1 • IL6R • IL6ST • MB • TP53

Evaluation of Background Kidney Parenchyma in Post Neoadjuvant Nephrectomy for Renal Cell Carcinoma (USCAP 2026) - "TKIs were used in 57% (e.g., lenvatinib, axitinib, cabozantinib); ICIs in 90% (pembrolizumab, nivolumab, ipilimumab), and 50% received dual ICI... Neoadjuvant therapy expands surgical options for RCC but introduces nephrotoxicity risks. In our cohort, 7.5% of cases showed histologic features suspicious for ICI-related nephritis. Careful evaluation of background parenchyma is essential, especially for signs of TMA and ICI-associated nephritis, which may affect long-term kidney function and recur contralaterally during post-nephrectomy chemotherapy protocols."

Clinical • Atherosclerosis • Clear Cell Renal Cell Carcinoma • Diabetes • Genito-urinary Cancer • Glomerulonephritis • Hypertension • Metabolic Disorders • Nephrology • Oncology • Renal Cell Carcinoma • Solid Tumor

Predicting targeted- and immunotherapeutic response outcomes in melanoma with single-cell Raman spectroscopy and AI. (PubMed, bioRxiv) - "Single-cell Raman spectroscopy combined with machine learning offers a scalable, prognostic platform to predict therapeutic resistance likelihood, with further potential to advance clinical, multi-omic biomarker efforts for melanoma. Our approach may improve first-and second-line therapy selection assessments for precision medicine by providing rapid, non-destructive prediction of therapeutic response based on cellular spectral profiles."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor

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

A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis. (ASCO-GU 2026) - P2 | "The CONTACT-02 trial showed efficacy of cabozantinib combined with the PD-L1 inhibitor atezolizumab in mCRPC...Baseline characteristics: 50% (12/24) had de novo metastatic disease, 91.7% (n=22) had bone metastases, 29.2% (n=7) bone-only disease, 16.7% (n=4) visceral metastases, 66.7% (n=16) received prior chemotherapy, and 25% (n=6) prior ¹⁷⁷Lu-PSMA-617 therapy... The CANOPY trial met its interim efficacy threshold, demonstrating activity of cabozantinib plus nivolumab in mCRPC patients. The combination showed manageable toxicity. The study continues to Stage 2 enrollment to further evaluate this promising combination therapy."

Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AXL