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.

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.

Despite the significant improvement in treatment outcomes with adjuvant imatinib therapy for patients, drug resistance remains a major challenge for GIST therapy...The OXPHOS pathway is a promising therapeutic target in combination with TKI against sensitive KIT/PDGFRA mutants. Comprehensive understanding of the above resistance mechanisms, experimental drugs/strategies and metabolic changes is critical to implement the proper therapy strategy and improve the clinical therapy outcomes for GIST.

This case underscores the necessity of total gastrectomy with lymph node dissection due to the high incidence of metastasis in GISTs associated with Carney's triad. Further research is required to determine the optimal extent of lymph node dissection in such cases.

The BDP conferred almost complete resistance to cell death induced by imatinib in CML stem and progenitor cells (LSPCs). Using BH3 profiling, we identified a novel therapeutic vulnerability of BDP LSPCs to MCL-1 antagonists, which we confirmed in primary human LSPCs, and in vivo. Our findings demonstrate the impact of human polymorphisms on the survival of LSPCs and highlight their potential as companion diagnostics for tailored therapies.

Our findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment.

In addition, depletion of PCIF1 sensitizes RCC to sunitinib treatment. This study highlights the intricate interplay between m6Am modification, phosphatidic acid metabolism, and mitochondrial dynamics, offering a promising therapeutic avenue for RCC.

P=N/A, N=787, Enrolling by invitation, Poitiers University Hospital

These findings demonstrate the role of BCAA/BCAT1 signaling in cancer development and suggest that targeting BCAA/BCAT1 signaling is a potential strategy for interfering with TKI-resistant CML.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN characterized by reciprocal translocation in the ABL1 and BCR region of chromosomes 9 and 22 respectively. We report a case of CML who presented to us with acute ischemic stroke and subsequently was diagnosed as CML transformed to the promyelocytic blast phase. She was successfully treated with dasatinib along with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).

55% (42/77) of liquid samples with a KIT -driver mutation had a co-occurring imatinib-resistant alteration, and a minority of cases harbored non- KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations... Known driver and TKI-resistant mutations are identified in liquid biopsies of patients with GIST, with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification of GIST during the medical management of advanced disease.

Analysis of annexin V labelling demonstrated that combination of IMA with betulinic acid enhances the inhibition on cell proliferation via apoptosis pathway, with caspases 3/7 activation after 24 hours of treatment, and inhibition of the STAT5/Survivin pathway, decreasing cell viability. The combination of natural products and IMA on a multidrug-resistant leukemia cell line is a promising strategy for CML treatment.

Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines.

The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months...Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT.

P2; Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009.

The last treatments received prior to the NEC-like transformation included PRRT (n = 3), somatostatin analog, everolimus, sunitinib (n = 1 each), and alkylating agents (n = 2). These findings are most likely attributable to the novel TP53 mutation, which was detected in all nine cases at the last evaluation. However, none of the cases exhibited a complete transformation to a typical NEC, as the tumors retained partial histological and genetic features of NETs.

Linifanib was a potential drug for high-risk populations...A nomogram provided a clinical practice reference. We constructed an HPRGS for HCC, which can accurately predict OS and guide the treatment decisions for patients with HCC.

P=N/A, N=168, Completed, First Affiliated Hospital, Sun Yat-Sen University

P1/2, N=88, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Apr 2024

The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first-line treatment for metastatic GIST...B7-H3 is expressed at a particularly high rate in GISTs. This suggests that B7-H3 might operate as part of an immune checkpoint in GISTs.

In IMmotion151, MTC2-metastasis was significantly associated with better PFS on sunitinib (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.32-8.69; p = 0.01) in comparison to MTC2-primary (HR 0.95, 95% CI 0.65-1.38; p = 0.80; pinteraction = 0.02). Evaluation of known RNA signatures in the CheckMate trials revealed that JAVELIN-metastasis was associated with better PFS on ICI (HR 0.77, 95% CI 0.62-0.97; p = 0.03) in comparison to JAVELIN-primary (HR 1.04, 95% CI 0.91-1.19; p = 0.56; pinteraction = 0.02). These results indicate that tissue site may be a relevant confounder in biomarker analyses.

Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

Furthermore, we discovered that TRIM37 mediates the degradation of SMARCC2 via ubiquitin-proteasome pathways, thereby further activating the Wnt signaling pathway. In conclusion, this study not only sheds light on the biological role of TRIM37 in RCC progression but also identifies a potential molecular target for therapeutic intervention in RCC patients.

He was treated with surgical resection with negative margins and imatinib therapy. Postoperative surveillance showed no evidence of malignancy and the patient experienced a positive response to treatment with stable hemoglobin levels and significant weight gain.

We describe a 26-year-old female with a background of metastatic paraganglioma harboring a pathogenic SDHB variant, requiring sunitinib, which was withheld to facilitate the safe conception and delivery of a healthy baby...Many of the treatment modalities for metastatic paraganglioma, including tyrosine kinase inhibitors, can affect fertility or cannot be utilized in pregnancy, necessitating the temporary suspension of these treatments. This case exemplifies that careful clinical and biochemical monitoring during pregnancy is required to avoid maternal and fetal harm while balancing the risk of disease progression off treatment.