imatinib

The patient received high-dose cytarabine over three cycles, developed febrile neutropenia requiring amikacin, and was subsequently started on imatinib 400 mg in view of the BCR-ABL1 positivity. What makes this case worth reporting is the convergence of three issues that each present their own challenges: establishing a diagnosis of de novo AML rather than CML in blast crisis, managing an already aggressive disease made more so by a complex karyotype, and deciding on the role of tyrosine kinase inhibitors in a disease setting where their use is not yet standardized. Detailed cytogenetic workup proved critical in navigating all three.

Furthermore, in PDX model established using AML cells from Gilteritinib-resistant patients, the degrader showed significantly superior therapeutic efficacy compared to the combination treatment of Gilteritinib and Imatinib. As a candidate drug molecule, this degrader exhibits promising potential for clinical translation.

After the first TFR attempt, major molecular response (MMR) was lost, and ponatinib was initiated but discontinued because of cerebral infarction. Imatinib was reintroduced, leading to the reachievement of a deep molecular response. This case underscores the importance of careful patient selection and long-term molecular monitoring following TFR attempts, including those involving novel TKIs such as asciminib.

We describe a case of complete and durable remission achieved with imatinib monotherapy in an unresectable mesenteric desmoid tumour with the patient remaining disease-free at 10 years. This case highlights the potential for long-term complete response and underscores the need for prospective data to guide treatment duration and cessation criteria.

The landscape of asciminib resistance is broader and more complex than previously appreciated, involving mutations across multiple domains that disrupt ABL1 autoinhibition. Epistasis between mutations acquired during sequential therapies can create unexpected and potent resistance. However, these diverse genetic resistance mechanisms converge on a single biophysical measurement of the openness of the active ABL1 conformation. This provides a unified framework for understanding asciminib resistance and underscores the need for routine clinical resistance monitoring to include the SH3 and SH2 domains in first line and later line therapy.

Among the synthesized molecules, F-4 demonstrated the strongest activity against K562 cells with an IC50 value of 6.85 µM, close to that observed for imatinib (IC50 = 5.20 µM)... The findings identify F-4 as a promising new thiazolone-derived scaffold with selective anti-CML activity and notable ABL TK inhibitory potential. Additional structural optimization may further enhance its binding characteristics and therapeutic efficacy.

The introduction of imatinib established proof of principle for oncogene-targeted therapy, leading to sustained survival improvements...More recently, the development of the allosteric inhibitor asciminib introduced a novel mechanism of action and expanded therapeutic options for pretreated patients...Thus, CML represents a unique model of translational oncology, demonstrating how mechanistic insight can drive therapeutic innovation. Future strategies will focus on increasing TFR rates, overcoming resistance, targeting leukemic stem cells, and improving global access to therapy and monitoring, with the ultimate aim of achieving functional cure in the majority of patients.

Ferrocene-based analogues can sustain stable ABL1 binding via non-classical interaction networks independent of hinge recognition. The clear distinction between active compounds and the inactive analogue 15e supports the robustness of the proposed binding mode and provides a structural basis for their reported cytotoxic activity. These findings support further experimental evaluation of ferrocene-containing scaffolds as potential BCR-ABL1 inhibitors.

In summary, we developed a novel characterization of lactylation-related clusters using single-cell sequencing technology. This study provided insights into the prognostic significance of lactate metabolism-related genes in GBM.

To address this, we performed proteome and phosphoproteome profiling of 12 MM cell line models, comprising four parental lines (AMO-1, ARH77, L363, and RPMI8226) paired with lines that acquired resistance to bortezomib (BTZ) or carfilzomib (CFZ). Beyond known adaptations such as the overexpression of the PI target PSMB5 and the drug efflux transporter ABCB1, we identified the oxidoreductases NQO1 and NQO2 as significantly upregulated proteins under chronic proteotoxic stress across several models. Pharmacological follow up in PI resistant AMO-1 cells showed that NQO2 inhibition by imatinib fully restored CFZ sensitivity, validating NQO2 as a contributor to resistance formation in this model system.

SerpinB9 overexpression is associated with fibrosarcomatous features in DFSP and may represent a candidate prognosis biomarker. The SF3B/SERPINB9 axis is a potential therapeutic vulnerability, particularly in FS-DFSP. NK cell- and macrophage-related signatures were evident in DFSP tumor microenvironment, warranting further functional studies.

P=N/A, N=1000, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting