imatinib

In light of the lack of metastatic dissemination and the patient's advanced age, targeted therapy with imatinib was commenced, leading to the elimination of hypoglycemia episodes. This case underscores the necessity of incorporating NICTH into the differential diagnosis of hypoglycemia in non-diabetic individuals, particularly when a tumor is present. Timely identification and focused intervention of the underlying neoplasm can result in positive outcomes.

This study describes a novel mechanism of direct bone marrow-mediated protection of leukemic cells from imatinib/TKI, related to transfer of metabolic proteins leading to higher activity of TCA cycle, metabolic plasticity and adaptation. Targeting the stroma-driven TCA cycle-related metabolism combined with imatinib presents a promising strategy to achieve therapeutic efficacy to overcome bone marrow microenvironment-mediated protection in CML.

These subtypes exhibited distinct drug sensitivities (C1 sensitive to panobinostat, MK-2206, 17-AAG; C2 sensitive to venetoclax) and predicted immunotherapy responses (C1 potentially benefiting more from anti-PD-1)...Crucially, aberrant PKM2 overexpression was linked to imatinib (IM) resistance...To mitigate vMO toxicity, IL3-Lamp2b-engineered exosomes were developed, demonstrating efficient vMO loading, targeted delivery to leukemia cells, potent PKM splicing correction, significant IM resistance reversal, and minimal stromal cell toxicity. This work defines glycolysis-based AML subtypes with therapeutic implications and establishes engineered exosome-delivered vMO as a promising strategy to overcome drug resistance in hyper-glycolytic myeloid leukemia.

Thus, our findings uncover a novel ERK-mTOR-axis for upregulation of proteasomal degradation of XIAP which could be targeted to overcome Imatinib-resistance by combinatorial inhibition of mTOR and XIAP in CML. This study holds the promise of a new therapeutic strategy for overcoming drug resistance in cancer.

Despite substantial advances, secondary mutations and reactivation of oncogenic signaling remain major challenges. This narrative review integrates data from clinical, preclinical, and real-world studies to update the current understanding of targeted therapies in cutaneous melanoma and highlight ongoing research aimed at overcoming resistance and optimizing personalized treatment strategies.

Using a 73-gene panel, we characterized the molecular characteristics of GISTs and revealed a correlation with their clinical features. Moreover, KIT/PDGFRA-dependent and KIT/PDGFRA-independent mechanisms underlying resistance to imatinib were explored. Overall, our 73-gene panel is sufficient for clinical application in cases of GISTs.

In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Peritumoral CD117 immunopositive mast cell density in prostatic adenocarcinoma correlates with the new Gleason score. It may be useful in patient selection for future trials of imatinib for low-grade prostatic adenocarcinoma.

Instead of neoadjuvant therapeutic options for wild-type (WT) NF1-related GIST, surgical resection remains the most advantageous treatment. The efficacy of tyrosine kinase inhibition and other chemotherapies tailored for WT GIST is currently untenable and warrants increased clinical trials and exploration of WT pathogenesis concerning NF1 to support Imatinib-sensitive patients.

Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

Drug sensitivity analysis revealed GW.441756, imatinib, and WH.4.023 were more effective in the low-risk group, with varying sensitivities to other drugs in the high-risk group. The qRT-PCR, WB, and IHC results matched the bioinformatics analysis, showing upregulated ATP7B expression in BRCA, indicating the high prognostic potential of the identified genes. ADME-related prognostic genes (GSTM2, ADHFE1, ALDH2, NOS1, ATP7B, and ALDH3A1) are implicated in BRCA pathogenesis, suggesting new therapeutic strategies for BRCA treatment.

Platelet-derived growth factor receptor beta (PDGFRB)-rearranged myeloid/lymphoid neoplasms (MLNs) are rare hematologic malignancies typically responsive to tyrosine kinase inhibitors (TKIs) such as imatinib. The patient progressed to acute myeloid leukemia (AML) within 11 months despite sequential therapies including dasatinib and azacitidine-venetoclax, ultimately succumbing to sepsis. This case highlights the limitations of TKI monotherapy in MLNs with PDGFRB rearrangements and co-existing high-risk mutations, underscoring the importance of early molecular profiling and consideration of allogeneic hematopoietic stem cell transplantation in cases with poor risk features.