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.

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.

Asciminib was found to have excellent efficacy and safety therapeutic profiles. The lack of comprehensive reviews about asciminib, thus, the current study aimed to evaluate the clinical and preclinical evidence of the efficacy and safety of asciminib.

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.

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.

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.

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P=N/A, N=40, Not yet recruiting, Novartis Pharmaceuticals

P=N/A, N=112, Recruiting, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital; The First Affiliated Hospital of Nanjing Medical University, J

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.

These results confirmed that dasatinib is a potent chemotherapeutic drug which induces apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in bladder cancer cells.

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.

The optimum micelles exhibited a dramatic reduction in IRF5 expression and revealed a notably higher anti-inflammatory effect than either DB or psiRF5, as indicated by more IL-10 and less IL-6 and TNF-α production by LPS-stimulated RAW264.7 macrophages incubated with the co-delivery system. The resultant nanocarriers might be promising for more effective treatment of inflammatory diseases.

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.

To counteract monotherapy-induced tumor relapse, we assessed GSI-paclitaxel and dasatinib-paclitaxel combination treatments in NOTCH inhibitor-sensitive and -resistant TNBC xenotransplants, respectively. These distinct preventive combinations and second-line treatment option dependent on NOTCH1 and SOX2 expression in TNBC are able to induce tumor growth control and reduce metastatic burden.

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.

P1, N=24, Active, not recruiting, Il-Yang Pharm. Co., Ltd. | Not yet recruiting --> Active, not recruiting

P=N/A, N=168, Recruiting, Il-Yang Pharm. Co., Ltd.

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.

Asciminib has also been shown to have no clinically relevant effect on cardiac repolarization. Here, we review the clinical pharmacology data available to date for asciminib that supported its clinical development program and regulatory applications.

P3, N=199, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jun 2024 --> Apr 2026

P2, N=196, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Jan 2027 --> Oct 2027 | Trial primary completion date: Jan 2026 --> Sep 2025

In summary, the dual inhibition of GPX4 and BCR-ABL presents a promising therapeutic strategy to synergistically target blast cells and drug-insensitive LSCs in patients, offering potential avenues for advancing leukemia treatment.

P3, N=173, Recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: Apr 2025 --> Dec 2027 | Trial primary completion date: Jan 2025 --> Jun 2026

P2, N=50, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Further, nilotinib treatment did not affect the expression of genes associated with neuronal health and mitochondrial functioning. Taken together, our findings do not support the efficacy of nilotinib treatment for neuroprotection.

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.

Pharmacological inhibition of MDH2 in GSCs augmented efficacy of dasatinib, an orally bioavailable multi-kinase inhibitor, including PDGFRβ. Collectively, stem-like tumor cells reprogram their metabolism to induce changes in their epitranscriptomes and reveal possible therapeutic paradigms.

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.

It also exhibited lower tumor mutation burden, mRNAsi, and EREG-mRNAsi and reduced sensitivity to other chemotherapy drugs, except dasatinib. These findings serve as a valuable indicator for personalized treatment strategies and clinical stratification in managing patients with EOC. Additionally, our study will serve as a foundation for future mechanistic research to explore the association between the ubiquitin-proteasome pathway and EOC.

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.

Overall, our findings indicate the prevalence and impact of new ABL1 KD mutations in BCR::ABL1-positive ALL patients, highlighting the necessity for effective therapies targetingthese mutations.

The study concluded that dasatinib treatment improved response in CML patients with decreased Treg cells. Dasatinib reduces Treg-mediated immunological suppression, reducing CTLA-4 and TGF-β1 levels.

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.

The results imply that MEF2C could be a valuable indicator for predicting outcomes and a possible target for immunotherapy for LUAD patients.

Two compounds, namely, radotinib and capmatinib, were identified as top compounds using molecular docking. The Western blot analysis assay showed that the phosphorylation level of STAT3 was significantly decreased upon radotinib treatment. Taken together, our findings suggest that radotinib, which is currently used in the treatment of chronic myeloid leukemia (CML), could be considered as a potential candidate for repurposing in the treatment of HCC.

Currently, ponatinib is the only approved tyrosine kinase inhibitor (TKI) that is effective for Ph-positive ALL with the T315I mutation...is a retrospective observational study, it offers prospects for the efficacy of chemotherapy combined with the novel third-generation TKI, olverembatinib, in these conditions, which may be validated in future prospective clinical trials...Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19804.

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