Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2. Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.

Finally, we highlight some of the ongoing studies that test quizartinib in patients with FLT3-ITD-positive AML, patients with FLT3-ITD-negative AML, in both the first-line and R/R settings, in patients fit or unfit for intensive chemotherapy, including studies for quizartinib-based combination with other compounds such as decitabine and venetoclax. Future research should aim to further optimize the clinical value of quizartinib and explore its use in additional clinical settings, which could be achieved by testing quizartinib with other drugs, better characterization of the mechanisms of resistance, identification of the role of quizartinib as a maintenance therapy after allo-HCT, and investigating quizartinib in patients with FLT3-ITD-negative AML.

PSMA-encoding FOLH1 gene expression correlates with neoangiogenesis and predicts PFS in m-ccRCC patients treated with sunitinib TKI, suggesting that PSMA PET could be explored as a noninvasive biomarker for guiding CST choice (IO/IO or IO/VEGFi) as well as prediction of treatment response to VEGFi in m-ccRCC patients.

Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.

H&E staining of major organs revealed no signs of damage, indicating the biosafety of St/siVEGFR-2@PCN-224@HA. The prepared St/siVEGFR-2@PCN-224@HA system enables triple inhibition of tumor growth via a combination of targeted therapy and genetic and photodynamic therapy to enhance the therapeutic effects on RCC.

Collectively, GFPT2 is potentially useful as a biomarker for prognostic prediction and immune infiltration in a variety of malignancies ,and could lead to exciting new approaches to personalized oncotherapy.

Our results suggest different immunosuppressive effects of these three FLT3i and may, therefore, provide an additional rationale for optimal maintenance therapy after alloHSCT of FLT3-positive AML patients to prevent infectious complications and GvHD mediated by DCs.

Transcriptomic analysis of these resistant organoids identified key pathways related to KRAS signaling, inflammation, and epithelial-mesenchymal transition (EMT), revealing potential targets for overcoming Lenvatinib resistance. This study provides valuable insights into MASH-related HCC progression and drug resistance, offering a model for further therapeutic research.

P2, N=43, Active, not recruiting, National Cancer Center Hospital East | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2025 --> Aug 2026

Furthermore, STAMBPL1 silencing and the tyrosine kinase inhibitor (TKI) sunitinib also exhibited a synergistic effect on the suppression of KIRC. Collectively, targeting the STAMBPL1/TRIM21/AXL axis can decrease mesenchymal phenotype and potentiate anti-tumor efficacy of cancer therapy.

P2, N=15, Active, not recruiting, National Cancer Institute (NCI) | N=40 --> 15 | Trial completion date: Sep 2027 --> Nov 2025 | Trial primary completion date: Sep 2027 --> Sep 2024

Finally, we recommended KGs-guided four repurposable drug molecules (Fluoxetine, Vatalanib, TGX221 and RO3306) against GBM through molecular docking, drug likeness, ADMET analyses and molecular dynamics simulation studies. Thus, the discoveries of this study could serve as valuable resources for wet-lab experiments in order to take a proper treatment plan against GBM.

P2, N=603, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Our findings suggest lenvatinib is a valuable treatment option for patients with HCC recurrence after LT.

Based on the preclinical characterization of SKLB1028 metabolism, three drug-drug interaction clinical studies were performed to investigate the effects of itraconazole, rifampin (CYP3A4 inhibitor and inducer, respectively), and gemfibrozil (CYP2C8 inhibitor) on the metabolism of SKLB1028. Co-administration with rifampin reduced the AUC of SKLB1028 by ~30%, while the Cmax did not change significantly. All treatments were well tolerated in all three studies.

P1/2, N=380, Not yet recruiting, Shanghai Runshi Pharmaceutical Technology Co., Ltd

P3, N=328, Not yet recruiting, Affiliated Hospital of Guangdong Medical University; Affiliated Hospital of Guangdong Medical University

P2, N=30, Not yet recruiting, Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital; Fujian Cancer Hospital

P2, N=38, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=46, Not yet recruiting, Cancer Hospital, Chinese Academy of Medical Sciences; Cancer Hospital, Chinese Academy of Medical Sciences

P2, N=68, Not yet recruiting, Harbin Medical University Cancer Hospital; Harbin Medical University Cancer Hospital

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital); The First Affiliated Hospital of Nanjing Medical University

P2, N=58, Not yet recruiting, Xuancheng People's Hospital; Xuancheng People's Hospital of Anhui Province

P1/2, N=62, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=36, Recruiting, The First Affiliated Hospital of Dalian Medical University; The First Affiliated Hospital of Dalian Medical University | Not yet recruiting --> Recruiting

P1, N=19, Completed, Shanghai Runshi Pharmaceutical Technology Co., Ltd | Not yet recruiting --> Completed

Compound 20b presents as a promising anti-proliferative agent targeting VEGFR-2. Also, this comprehensive investigation underscores the potential of 2,3-dihydro-1,3,4-thiadiazole derivatives as promising candidates for further development in anti-cancer research.

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

(Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

Activation of Nrf2 signaling by LR HCC cell-derived exosomal miR-301a-3p skewed the transformation of macrophages to the M2 phenotype. Our study provides new findings on the role of miR-301a-3p, suggesting it is a promising therapeutic target to improve HCC lenvatinib resistance.

The temporal dynamics of these effects demonstrated greater significance than dose-dependent responses. Both VEGFi and VEGFRi significantly augmented the risk of immune-mediated, blood pressure-related adverse events, with VEGFRi inducing a more rapid and pronounced onset of blood pressure elevation and a higher incidence of immune-related, blood pressure-associated adverse events compared to VEGFi.

We then profiled a wet-lab cohort of 37 FLT3-mut AML patients treated either with Midostaurin plus chemotherapy (M) or Gilteritinib (G) at Bologna Hematology Institute by using the PanCancer IO 360 Panel (NanoString Technologies, San Diego, CA). This study provides evidence that FLT3 mutational status is associated with a unique T-cell activation profile and AML maturation state, and that T/NK cell-associated genes correlate with response to FLT3i. Our RNA metric of FLT3 mutational status could be utilized to refine patient stratification in future clinical trials. S.R.

P=N/A, N=39, Recruiting, Jinling Hospital, China

Our findings clarified the adverse outcome induced by high expression of ITGA5 in ccRCC patients. In vitro experiments and bioinformatical analysis identified ITGA5 function as predominantly cell proliferation, migration, angiogenesis, and macrophage recruitment. Further, we predicted immune infiltration and medication sensitivity regulation by ITGA5 and proposed a joint use of ITGA5 inhibitors and anti-angiogenetic drugs as a potential potent therapeutic strategy.

Lastly, the drug sensitivity analysis revealed that the BLCA cells in the high-risk group showed an increased sensitivity to cisplatin, sunitinib, cetuximab, axitinib, docetaxel, saracatinib, vinblastine and pazopanib compared with those in the low-risk group. According to the Quantitative real time PCR results, we found that five lncRNAs of the risk model were more highly expressed in BCa cell lines than human immortalized uroepithelial cell line. The disulfidptosis-related lncRNA risk model has a valuable effect in assessing the prognosis of BLCA patients.

The combination regimen demonstrated promising efficacy in treating unresectable HCC, accompanied by manageable safety profiles. Furthermore, the results of this investigation suggest that AFP holds promise as predictive biomarkers for this treatment strategy.

P2, N=38, Not yet recruiting, National Cancer Center, Japan

P2, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial primary completion date: Aug 2024 --> Dec 2024

P2, N=39, Completed, Nanfang Hospital, Southern Medical University | Recruiting --> Completed

P2, N=58, Active, not recruiting, The Netherlands Cancer Institute | Trial completion date: Mar 2025 --> Mar 2026

BAIAP2L2 inhibits the levels of reactive oxygen species (ROS) by regulating GABPB1, thereby promoting cancer properties in HCC and reducing the sensitivity of HCC to lenvatinib. In summary, this study elucidates the role and underlying mechanism of BAIAP2L2 in HCC, providing a potential biomarker and therapeutic target for this disease.

STM2457 treatment attenuated the serine synthesis pathway, induced oxidative stress, and sensitized HCC cells to sorafenib and lenvatinib treatments. In conclusion, our findings suggest that targeting m6A could be a potential therapeutic strategy for HCC treatment.