Iclusig (ponatinib)

Furthermore, ponatinib increases chimeric antigen receptor (CAR) TSCM cells by reducing CAR T cell exhaustion, resulting in durable antitumor efficacy. Our results thus implicate ponatinib as therapeutic immunomodulator, inducing TSCM cells for improved antitumor T cell activity.

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

This case highlights the clinical significance of multilineage Ph+ ALL and its distinct biological background, thereby underscoring caution with TKI discontinuation despite deep NGS MRD-negativity, and may support continued TKI therapy in this setting.

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.

Essential dynamics and free-energy landscape analyses, followed by MM-PBSA and per-residue analyses, supported the thermodynamic stability and favorable binding energetics of the complexes. Collectively, these findings nominate Ponatinib and Lapatinib as promising repurposing candidates for subsequent biochemical and cellular validation as AURKB inhibitors.

P3, N=348, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=25, Suspended, University of Chicago | Recruiting --> Suspended

P2, N=84, Recruiting, National Cancer Institute (NCI) | N=64 --> 84

All TKIs are not recommended during the first trimester due to their risk of teratogenesis, but imatinib and nilotinib may be cautiously used from Weeks 16-18 onward. Non-TKI therapies, such as hydroxyurea and interferon-α, are considered safe throughout pregnancy. Data on ponatinib and asciminib remain insufficient to allow the safe use of these agents during pregnancy. Future research should aim to improve treatment-free remission rates through novel agents and combination strategies to allow a higher proportion of younger patients to discontinue therapy. Clinicians should always counsel women on pregnancy risks during therapy while reassuring male patients of TKI safety when fathering children.

GATA-1 knockdown eliminated DUSP21's effects on erythroid differentiation and ponatinib sensitivity in K562 and K562R cells. Collectively, these findings suggest that DUSP21 acts as a positive regulator of erythroid differentiation in CML cells, and its overexpression sensitizes imatinib-resistant CML cells to ponatinib via GATA-1-mediated erythroid differentiation.

Among four prioritized compounds, Ponatinib demonstrated the most favorable binding free energy, while Pimavanserin exhibited stable conformational behavior during simulation. These findings provide an in-silico prioritization framework for potential KIF11-targeting compounds in GBM. Experimental validation in relevant cellular and in vivo models will be required to determine biological and therapeutic relevance.

For resistance, assessment of BCR::ABL1 mutations is essential, and second-line agents should be chosen according to the initial TKI and mutation sensitivity. This article summarizes the criteria and timing for switching to second-line therapy and key considerations for selecting and managing second-line TKIs, and briefly reviews the evidence for asciminib and ponatinib in second-line and later settings.