Overexpression of MICAL-L2 stimulated cell migration, proliferation, and rendered KIRC cells insensitive to sunitinib and everolimus, two traditional therapies for KIRC. Furthermore, MICAL-L2 overexpression accelerated cancer progression and resistance to therapy in KIRC cells by interacting with its downstream regulator α-actinin-4 (ACTN4) in a Rab13-dependent manner, which reduced the degradation of ACTN4, leading to increased Vimentin expression. All these findings indicate that MICAL-L2 plays a crucial role in the progression of KIRC and suggest that MICAL-L2 may serve as a potential therapeutic target for KIRC treatment.

The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.

Molecular docking studies with Aurora-A Kinase revealed binding behaviors similar to the co-crystallized ligand sunitinib. Finally, this scaffold exhibits cytotoxic activity via apoptosis, enzyme downregulation, and suppression of cell division.

Sunitinib for c-KIT mutations did not meet the primary end point, but in this small sample size, a potential signal cannot be ruled out. Rate of eligible c-KIT mutations was low, affecting accrual to this arm.

Notably, the IKBKE inhibitor CYT387 restores sunitinib sensitivity in RCC cells by downregulating RRM2 expression. Collectively, these results indicate that inhibition of IKBKE restrains RCC progression and enhances sunitinib sensitivity by downregulating RRM2 through the RRM2-AKT pathway, suggesting that IKBKE may be a potential therapeutic target for RCC.

P3, N=184, Completed, Chipscreen Biosciences, Ltd. | Recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2024 --> Apr 2024

All patients with Philadelphia chromosomes-positive ALL received imatinib concomitantly with chemotherapy...Detection of IgH clonality after second cycle of chemotherapy correlates with inferior survival in B-ALL. Therefore, those patients should be considered for subsequent treatments, such as allogeneic stem cell transplantation or novel monoclonal antibody.

The standard treatment includes surgery and imatinib for metastatic cases; however, resistance to tyrosine kinase inhibitors remains a significant hurdle, especially in pediatric and wildtype GISTs. This highlights the need for advanced therapeutic strategies and emphasizes the importance of molecular profiling in guiding treatment decisions and improving outcomes for GIST patients.

on key kinase signaling pathways was further studied in the ER+ breast cancer (MCF-7) and bcr-abl+ leukemic (AR-230) in vitro tumor models in a comparative manner to the reference drugs tamoxifen and imatinib, respectively. Inhibition of the JAK/STAT signaling pathway was outlined as a prominent mechanism in the antileukemic activity against the Ph+ AR-230 in vitro model, whereas recruitment and activation of the extrinsic apoptotic pathway was established in the MCF-7 cells.

P3, N=180, Recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Dec 2024 --> Dec 2025

The research findings indicate that sunitinib may induce cytotoxic effects in hepatocytes through mechanisms involving oxidative stress, endoplasmic reticulum stress, and mitochondrial damage. However, in the kidney, the toxicity mechanism is different from that of liver, and the endoplasmic reticulum stress does not seem to be involved in this mechanism.

The article Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials, received most citations...The research on DFSP faces several clinical challenges. This study provides novel insights into future research directions and scientific decisions for DFSP.

Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the top100/base (600 structures), in comparison with the commercial drug imatinib, showed that only nine exhibited the desired properties...Considering future in vitro or in vivo assays, we elaborated the theoretical synthetic routes of the promising compounds identified in the present study. Based on our in silico findings, the selected ligands show promise for future studies in developing chronic myeloid leukemia treatments.

NU.1025 and imatinib were identified as potential inhibitors for SPIB and PLK1, respectively... The ANRS can act as an independent prognostic indicator for BC patients, providing significant guidance for the implementation of chemotherapy and immunotherapy in these patients. Additionally, PLK1 has emerged as a potential blood-based diagnostic marker for breast cancer patients.

This splice-site PDGFRB variant favors the development of myofibroma featuring an acquired oncogenic variant in the same gene and resistance to targeted therapy.

Our research suggests Hsa_circ_0072732 enhanced renal cell carcinoma sunitinib resistance by inhibiting ferroptosis through miR-548b-3p/SLC7A11.

Non-Fickian diffusion at pH 5.5 resulted in sustained in-vitro drug release, with no initial burst. In-vivo investigations using albino Wistar rats suggest pharmacokinetic properties for produced nanoparticles, whereas histopathological examinations assess acute toxicity.

These results highlight the ability of Imatinib to suppress EMT through modulation of the Notch signalling pathway, offering a novel therapeutic avenue for breast cancer treatment. Overall, Imatinib demonstrates considerable potential for repurposing in breast cancer management by targeting critical oncogenic pathways involved in EMT and cancer progression.

YAP expression serves as a predictive marker of recurrence for GIST patients with curative resection, highlighting its potential as a novel therapeutic target that warrants further investigation.

According to the Genomics of Drug Sensitivity in Cancer (GDSC), patients with a high IRS had a decreased IC50 for sunitinib, which is the first-line treatment for ccRCC patients. As a result, the immune characteristics of the microenvironment of ccRCC tumours have been explored, and a signature has been constructed. Analysis demonstrated that our signature could effectively predict prognosis and immunotherapy response rate.

P2, N=9, Terminated, Chipscreen Biosciences, Ltd. | N=38 --> 9 | Recruiting --> Terminated; During the enrollment period of this project, due to the increasing proportion of patients receiving capecitabine adjuvant therapy and the large number of trials competing for the same number of lines in various centers

The combination of MST-312 and imatinib shows potential as a CML therapy. However, further research and clinical trials are necessary to validate these findings and determine their clinical relevance.

Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi-target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

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.

We validated the expression levels of these four genes using clinical samples and confirmed through cell experiments that targeted inhibition of IGFBP2 effectively suppressed proliferation of resistant CML cells, promoted apoptosis, and enhanced therapeutic sensitivity to imatinib...The identification of molecular subtypes provides valuable insights into assessing individual patients' biological characteristics for guiding clinical treatment decisions. Additionally, IGFBP2 has emerged as a promising therapeutic target for therapy-resistant cases of CML.

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.

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.

Additionally, overexpression of LPAR1 restrained the biological function of miR-429 on imatinib chemoresistance. MiR-429 partly sensitized glioma cells to imatinib via downregulation LPAR1, which might provide an approach to overcome imatinib chemoresistance during glioma treatment.

Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.

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

Their conjugation with the drugs Irinotecan, Imatinib, and Methotrexate was also confirmed using UV-Vis, FTIR, and Dynamic light scattering (DLS). The result of the methylthiazol tetrazolium (MTT) assay showed that conjugated AgNPs and AuNPs with Irinotecan had a higher toxic effect on the A549 cancer cell line than AgNPs and AuNPs conjugated with Imatinib. This study provides a promising avenue for further investigation and development of nanoparticle-drug conjugates as a potential cancer immunotherapy strategy.

Thirty-five patients will be recruited with an interim analysis planned after recruitment of 20 patients. The study is open for inclusion and 4 patients have been included as of 10th of June 2024.

In addition to BCR-ABLIS level, HT of BCR-ABLIS can be used as another important predictor of treatment efficacy in CML patients. The combination of BCR-ABLIS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.

Additionally, we found that ATL-I could decrease the level of EPAS1, which was upregulated in sunitinib-resistant cells, thus reversing sunitinib resistance. Collectively, our findings demonstrate that ATL-I is a robust antiangiogenic and antitumor lead compound with potential clinical application for ccRCC therapy.

The identified molecules were found to be effective and significantly bound with the PDGFRβ kinase domain. Overall, our findings demonstrate that these small drug-like compounds can be beneficial tools in studying the properties of PDGFRβ and can play a crucial role in the therapeutic development of cancers and other associated diseases.

He was found to be positive for BCR-ABL by reverse transcription polymerase chain reaction (RT-PCR), thus confirming the diagnosis of CML. He received imatinib 400 mg/day and subsequently experienced resolution of symptoms and complete hematological response by the 12th week of therapy.

Management included observation in 6 (46.3%), hydroxyurea in 3 (23.1%), imatinib in 3 (23.1%) and Interferon-α (IFN-α) in 1 (7.7%) patients. Effective management of newly diagnosed CML-CP during pregnancy is contingent on the trimester of presentation. Further research and collaboration are warranted to develop standardised guidelines for managing pregnancy-associated CML, particularly in LMICs.

Our findings reveal a significantly higher proportion of Tregs and PD-1 + CD8 T-cells in patients with CML-CP compared to healthy controls, notably diminished following imatinib treatment. These observations suggest the potential for immunotherapy as a promising approach to managing immune exhaustion in CML patients.

Thirty five (92%) patients were treated with imatinib at diagnosis...On multivariate analysis, none of these factors were found to be significant. This retrospective study suggests that for CML CP patients achieving deep molecular response, discontinuing TKI therapy in real-world settings may be feasible while potentially achieving comparable outcomes.

We also found that NK-128 inhibits colony formation by CD34+ CML cells isolated from the bone marrow of untreated CML patients. Taken together, these findings suggest that targeting OXPHOS is a beneficial approach to eliminating CML-LSCs, and may improve the treatment of CML.

The results showed lower expression of HOTAIR and PTGS2 in CML patients. The HOTAIR expression is inversely associated with BCR::ABL1 expression in imatinib-treated CML patients, and to PTGS2 showing that CML patients with high BCR::ABL1 expression showed reduced PTGS2 expression.

In 3 cases, this increase reflected the occurrence or worsening of imatinib side effects. This case-series highlights the clinical impact of SARS-CoV-2 infection on the management of patients with GIST treated with imatinib.