imatinib

Since the introduction of imatinib in the early 21st century, the management of metastatic GIST has shifted from solely surgical intervention to a systemic, chronic disease management model centered on tyrosine kinase inhibitors (TKIs)...These challenges underscore the necessity of this review, which discusses current standard drug treatment strategies for advanced GIST, including sequential TKIs therapy and investigations into mechanisms of drug resistance. Finally, the review explores precise and actionable future directions for GIST drug development and clinical management, including mutation-stratified therapeutic sequencing, rational TKI-based combination regimens, and circulating tumor DNA (ctDNA)-guided real-time treatment monitoring and resistance surveillance.

Although less potent than the nanomolar-range reference drug Epothilone B (IC50 < 0.1 μM), rugulosin A showed submicromolar-to-low micromolar efficacy with notable selectivity toward cancer cells, which is considered significant for an unoptimized natural product scaffold. Its antiproliferative activity against K562 cells (GI50 = 3.69 μM), benchmarked against Imatinib (GI50 = 0.373 μM), also falls within the active range of natural product leads...Molecular docking revealed strong binding energies (-10.1, -9.8, and -11.0 kcal/mol), along with a stable molecular dynamics simulations data. These findings highlight rugulosin A (3) as a promising anticancer lead that modulates major apoptosis signaling pathways.

Aberrant B cell receptor signaling occurs in several B cell neoplasms including follicular lymphoma (treated with zanubrutinib, a BTK inhibitor), mantle cell lymphoma (acalabrutinib, pirtobrutinib, zanubrutinib), marginal zone lymphoma (zanubrutinib), chronic lymphocytic leukemia and small lymphocytic lymphoma (ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib), and Waldenström macroglobulinemia (ibrutinib, zanubrutinib)...Pirtobrutinib fails to form a covalent bond and is a reversible BTK inhibitor. The FDA-approvals of rilzabrutinib and remibrutinib (2025) represent the first nononcologic authorizations for BTK antagonists.

This case highlights a rare cytogenetic abnormality in CML characterized by acquired pericentric inversion of the derivative chromosome 9 associated with BCR and ABL1 codeletion. Such complex rearrangements likely reflect clonal evolution and may be associated with suboptimal response to first line imatinib therapy. Accurate discrimination between constitutional and acquired inv(9), together with detailed assessment of derivative chromosome 9 integrity, is essential for prognostic stratification. Comprehensive cytogenetic and molecular analyses remain critical for identifying uncommon secondary abnormalities that may influence therapeutic response and clinical outcome in CML.

P2, N=40, Completed, Asan Medical Center | Recruiting --> Completed

P3, N=450, Recruiting, GlaxoSmithKline

P1/2, N=48, Recruiting, Asan Medical Center | Not yet recruiting --> Recruiting

Among the compounds, 3b emerged as the most potent with a GI50 of 0.72 μM against HepG2, compared to Imatinib (GI50 = 1.92 μM)...Moreover, docking, MD simulation, and DFT also suggest IDO1 as the molecular target responsible for the observed immunomodulatory effects. Collectively, these results suggest further biological investigation to explore the translational potential of compound 3b.

P2, N=950, Completed, University of North Carolina, Chapel Hill | N=395 --> 950

P1/2, N=100, Recruiting, Cardiff University | Not yet recruiting --> Recruiting

P4, N=155, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2033 --> Apr 2026 | Trial primary completion date: Apr 2033 --> Apr 2026

Inhibition of PGK1 initiates autophagy in T315I-mutant chronic myeloid leukemia (CML) cells, thereby enhancing their sensitivity to first-generation Tyrosine Kinase Inhibitor (TKI) imatinib and third-generation TKI ponatinib. Notably, CPU-216 induces autophagy via VCP and Beclin 1 in CML-T315I cells, enhancing their responsiveness to TKIs. These discoveries propose a novel therapeutic strategy for T315I-mutant CML, underscoring the potential to develop targeted treatments that leverage the kinase functions of PGK1.