bosutinib

P2, N=17, Active, not recruiting, Baylor College of Medicine | N=100 --> 17 | Recruiting --> Active, not recruiting

BCR::ABL1 e6a3 demonstrated enhanced sensitivity to active-state selective inhibitors dasatinib and bosutinib, whereas BCR::ABL1 e6a3/T315I remained resistant. These data show that treatment with asciminib and ponatinib can select for mutations with notably elevated enzymatic activity, effectively targeted by an axitinib-based triple combination. These data highlight the remarkable mutability of the BCR::ABL1 kinase, including through novel isoforms and provides a strong rationale for the clinical assessment of a triple inhibitor combination as a strategy to overcome resistance to dual ponatinib and asciminib therapy.

These findings show reduced selective packaging of p-SRC into EVs shed by MDR cells (MDR-EVs), suggesting an important role for this protein in the MDR phenotype and its potential as a molecular target. Bosutinib, an SRC inhibitor, might be useful as a chemosensitizer of MDR cells.

During follow-up, improvements in tricuspid regurgitant pressure gradient, brain natriuretic peptide values, and hypertension were observed after reducing the dose of the same TKI, interrupting the TKI treatment, and switching from the newer-generation TKIs to imatinib (IM) or bosutinib (BOS). These findings highlight the importance of blood pressure control and cardiovascular monitoring for CVE prevention in high-risk CML patients. Switching to IM or BOS, TKI dose reduction, or treatment discontinuation was observed to be associated with improvement in cardiovascular parameters in selected patients achieving deep molecular response.

P=N/A, N=600, Recruiting, Pfizer | Active, not recruiting --> Recruiting

Drug sensitivity analysis revealed that UBE2D3-low tumors were more responsive to vincristine, bosutinib, and ambazone [median inhibitory concentration difference (IC50 diff.) P<0.01], supported by favorable molecular docking affinities. Correspondingly, its loss appears to correlate with advanced disease, an immunosuppressive tumor microenvironment (TME), and unfavorable prognosis. This potential role in modulating immune cell dynamics and drug sensitivity positions UBE2D3 as a promising biomarker for prognostication and personalized therapy selection in KIRC.

P3, N=406, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2028 --> Jan 2031

EVs from SRC inhibitor Bosutinib treated cells showed reduced effects on cell viability, migration, and invasion of MUC1 knockout cells as compared to EVs from untreated cells...Collectively, our findings identify a previously unrecognized role for MUC1 in influencing EV composition and function: influencing loading of oncogenic protein cargoes into EVs. Our data highlight a novel mechanism controlling tumor-specific EV cargo loading and demonstrate that oncogenic cargo in MUC1-associated EVs contributes to pancreatic cancer progression.

In Japan, five agents-imatinib (Glivec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), and STAMP inhibitor asciminib (Scemblix®)-are currently approved for first-line therapy. Looking forward, immunologic determinants of TFR and novel therapeutic approaches, including targeting CML stem cells with agents such as asciminib or demethylating drugs, may offer prospects for cure. This review summarizes the current evidence and practical considerations in selecting first-line therapy for chronic-phase CML, with a focus on optimizing long-term outcomes and advancing toward individualized and potentially curative strategies.

P3/4, N=136, Active, not recruiting, Stichting Radboud universitair medisch centrum | Not yet recruiting --> Active, not recruiting

P2, N=720, Recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jan 2026 --> Dec 2026

Mechanistically, Tus inhibited tolimidone-induced Lyn kinase activation and suppressed SP-and Tween 80-induced β-hexosaminidase release, exhibiting an inhibitory profile comparable to that of the Lyn/Btk antagonist bosutinib. Additionally, Tus attenuated the phosphorylation levels of MRGPRX2 downstream signal molecules, including Btk, PLCγ1, PKC, p38 MAPK, IκB-α and NF-κB (p65). In conclusion, Tus attenuates SP-and Tween 80-induced mast cell activation and pseudo-allergic reactions by targeting the Lyn/Btk/PLCγ1 and p38/NF-κB pathways, highlighting its therapeutic potential for pseudo-allergy.