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.

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=43, Completed, Georgetown University | Recruiting --> Completed | Trial completion date: Dec 2023 --> Apr 2025 | Trial primary completion date: Dec 2023 --> Apr 2025

P2, N=69, Recruiting, Korean Society of Hematology | 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.

P1, N=250, Recruiting, Enliven Therapeutics | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

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

P=N/A, N=200, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Cumulative MR4.0 and MR4.5 rates by week 48 were 42.3% and 26.5%, respectively, with some patients harboring baseline BCR::ABL1 mutations showing these responses. These real-world outcomes support the safety and effectiveness of asciminib for patients with resistant/intolerant CML.

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.

Moreover, the combination of Baf@NPs with PDCD1/PD-1 antibodies further enhanced anti-tumor immunity and improved tumor treatment. Together, our results identify a safe, highly effective and specific NLRP3 inflammasome agonist and underscore it enhances anti-tumor immunity by triggering the NLRP3 inflammasome in macrophages, providing a potential therapeutic strategy for tumor treatment.