While lenvatinib (LEN)-TACE offers the potential for good outcomes, local recurrence has not yet been adequately investigated...Local recurrence factors included LEN pretreatment, and Lip CT values were higher immediately after LEN-TACE. Thus, LEN-TACE after upfront LEN administration may increase the effectiveness of TACE.

Current AAT therapies comprise antibodies targeting VEGFs, tyrosine kinase inhibitors (TKi) (Sunitinib) that target neo-angiogenesis receptors, and competitive inhibitor receptors (Aflibercept) that trap VEGFA and PlGF...Despite these advances, ccRCC remains challenging to treat adequately. Thus, future research is imperative to better understand the biology and pathophysiology of RCC, the tumor microenvironment, and mechanisms of resistance, with the aim of developing new therapies.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2025

P3, N=412, Not yet recruiting, Hutchmed

(Trial registration: ClinicalTrials.gov, NCT03456804. Registration date: March 7, 2018).

However, its use is associated with significant bleeding risks, including rare but severe complications such as cerebellar hemorrhage. This case report presents a patient with mCRC who developed a cerebellar hemorrhage shortly after initiating fruquintinib therapy, highlighting the need for careful patient monitoring and individualized risk assessment to mitigate such serious adverse events.

Candidates identified using the GEM-GNN model were selected for in silico modeling using molecular dynamics simulations to further validate their efficacy. The GEM-GNN model enabled the identification of candidate compounds with potentially more favorable properties than the existing drug, axitinib, while achieving higher efficacy.

Notably, overexpression of TBC1D31 markedly increases the resistance of HCC cells to lenvatinib, whereas inhibition of the TBC1D31-EGFR axis can reverse this resistance phenotype. This study highlights that TBC1D31 at 8q24.13 is a new critical oncogene, uncovers a novel mechanism of EGFR activation in HCC, and proposes the potential strategies for treating HCC patients with TBC1D31 amplification or overexpression.

Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.

This case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.

These cells were cultured with axitinib or a multi-target TKI lenvatinib. Axitinib-induced senescent lung adenocarcinoma A549 cells were drastically lysed by ABT-263. In A549-xenografted mice, combination therapy with axitinib and ABT-263 significantly suppressed tumor growth with the induction of apoptotic cancer cells.

High expression levels of FAM202B correlated with increased resistance to sunitinib and enhanced responsiveness to immunotherapy, as evidenced by associations with tumour mutation burden, PDCD1, CTLA4 and TIDE scores. FAM210B exerts a complex influence on HCC, affecting tumour cell behaviour, metabolic pathways, the immune microenvironment and responses to therapy.

P2, N=38, Recruiting, Peking University

P1/2, N=37, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.

P2, N=62, Active, not recruiting, University of Southern California | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=30, Not yet recruiting, The First Hospital of Jilin University

Herein, we synthesized iRGD-modified pH-sensitive liposomal nanoparticles co-encapsulating lenvatinib (Len) and the small molecule PD-1/PD-L1 inhibitor BMS-202 (iRGD-lip@Len/BMS-202) to address issues related to inadequate tumor enrichment and distinct pharmacokinetics of these drugs. Collectively, the combination of Food and Drug Administration (FDA)-approved drugs with iRGD-modified liposomes presents a promising strategy for HCC treatment. Simultaneously, IVIM-MRI provides a non-invasive method to accurately predict the response to this nanodrug.

Tumor-bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC.

By revealing their structure-activity relationships, pharmacological actions, and clinical trials, small-molecule drugs can offer broad prospects for the development of new medications.

P=N/A, N=20, Not yet recruiting, Fujian Provincial Hospital

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2025 --> May 2026

In exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, reducing the ratio of BAX to Bcl-2, consistent with apoptosis resistance. These results provide a mechanism by which AQP1 can regulate PASMC fate.

Most HCC samples were sensitive to sunitinib. Our results offer a comprehensive view of the molecular landscape of HCC, highlighting the significance of the HH pathway and providing insight into focused treatments for HCC.

Downregulation of SIX1 attenuated nuclear translocation of DHX9 and abrogated the binding of DHX9 to ITGB1 promoter. Collectively, our results unveiled a new signal axis SIX1/ITGB1/FAK in KIRC and identified a novel therapeutic strategy for metastatic KIRC patients.

P2, N=35, Recruiting, Georgetown University | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

The present findings underscore the potential of lenvatinib as a promising therapeutic option in the treatment of gastric cancer. By elucidating its mechanism of action and identifying PDGFRB as a primary target, the present study may aid further clinical advancements.

P2, N=37, Active, not recruiting, Bai-Rong Xia | N=20 --> 37

P2, N=74, Recruiting, Anhui Provincial Cancer Hospital | N=50 --> 74

P2, N=400, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=28, Recruiting, Fujian Provincial Hospital

P4, N=78, Not yet recruiting, Takeda

P2, N=64, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Finally, sKGs-guided top-ranked three repurposable drug molecules (Digoxin, Imatinib, and Dovitinib) were recommended as the common treatment for both T2D and ccRCC by molecular docking and ADME/T analysis. Therefore, the results of this study may be useful for diagnosis and therapies of ccRCC patients who are also suffering from T2D.

Our study completely assesses the cytotoxic efficiency of pyrimidine-based derivatives 4-15 against various cancer cell lines, revealing derivatives 12 and 15 for their remarkable activity with GI50 values of 37 and 35 nM, respectively, when compared to the reference erlotinib (33 nM)...Additionally, an in vitro assessment of the novel targets' apoptotic potential revealed that both pro-apoptotic and antiapoptotic behaviors were promising, indicating that the apoptotic induction pathway is a strongly proposed action method for the newly developed targets. Finally, molecular docking experiments are elaborately discussed to corroborate the exact binding interactions of the most active hybrids 12 and 15 with the EGFR and VEGFR-2 active sites.

SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.

lenvatinib alone was more strongly associated with adrenal insufficiency than lenvatinib and pembrolizumab combination. FGFR4, PDGFRA, and KIT (Lenvatinib targets) are potentially linked to cholecystitis, cholangitis, and hepatic encephalopathy. We identified Lenvatinib-associated AEs and discovered new AEs that will be useful for clinical monitoring and risk assessment.

Cediranib and thalidomide effectively reduced tumor size over time. The accessibility of Evans Blue outside the tumor core continuously decreased over time. The vascular density was significantly decreased after treatment while the proportion of normal vessels remained unchanged over time. In contrast to histological studies, DCE-MRI did not tackle any significant change in hemodynamic parameters, in the core or margins of the tumor, whatever the parameter used or the pharmacokinetic model used. While cediranib and thalidomide were effective in decreasing the tumor size, they were ineffective in transiently increasing the delivery of agents in the core and the margins of the tumor.

The results of this proof-of-concept open-labeled clinical trial suggest that the CDP-based second-generation AI system-generated personalized therapeutic recommendations may improve the response to lenvatinib with manageable AEs. Prospective controlled studies are needed to determine the efficacy of this approach.

P2, N=50, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

P2, N=22, Recruiting, Emory University | Trial completion date: Aug 2024 --> Jan 2026 | Trial primary completion date: May 2024 --> Jan 2025