BCR (BCR Activator Of RhoGEF And GTPase)

P1, N=20, Recruiting, The First Affiliated Hospital of Soochow University | Active, not recruiting --> Recruiting | Trial primary completion date: Jul 2026 --> Nov 2025

The observed common spatial distribution of fNBP1 and BCR-ABL enhances the understanding of this protein complex's formation, suggesting a potential role for fNBP1 in CML development.

CML and PV exhibited distinct cytokine-driven transcriptional signatures, whereas ET and PMF exhibited minimal alterations. These findings support the clinical utility of NanoString technology for bone marrow specimens and highlight disease-specific immune pathways as potential diagnostic biomarkers in MPNs.

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

The selective HDAC6 inhibitor 7b induced sustained α-tubulin acetylation at lower concentrations than ricolinostat or nexturastat A. 7b reduced primary CML PBMC viability while sparing healthy PBMCs and was active in vivo...ISR activation occurred downstream of the autophagy disruption: rapamycin attenuated ISR activation, whereas ATG7 silencing intensified ISR signaling and apoptosis...The combination elicited immunogenic cell death markers: calreticulin exposure, ATP and HMGB1 release, elevated TNF-α, and reduced IL-8. These findings identify HDAC6-driven autophagy as a therapeutically exploitable vulnerability in CML that, when combined with asciminib, triggers ISR-dependent immunogenic apoptosis.

Furthermore, LO metabolically reprogram MSC and prime MSC towards differentiation into adipocytes capable of sustaining B-ALL cell growth. Thus, LO-educated MSC, and the adipocytes derived from them, support B-ALL cells by distinct mechanisms, and targeting of LO-mediated communication pathways to prevent B-ALL progression has potential for the development of novel adjuvant treatment strategies.

Chronic lymphocytic leukaemia (CLL) most commonly transforms into aggressive lymphoma; development of chronic myeloid leukaemia (CML) in a patient with CLL should prompt evaluation for an independent myeloid clone rather than presumed transformation.Myeloid neoplasms in patients with CLL may arise from therapy-related leukemogenesis or divergent evolution from a shared hematopoietic progenitor, highlighting the importance of molecular characterization.Management of coexisting CLL and CML requires individualized risk-benefit assessment, particularly in elderly patients with prior solid tumours and immune dysfunction.

P1, N=15, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Phase classification: P1/2 --> P1

P2, N=25, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

P2, N=25, Recruiting, University of Chicago | Suspended --> Recruiting | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2027 --> Mar 2028

P2, N=20, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2026 --> Jun 2026 | Trial primary completion date: Nov 2026 --> Jun 2026

The patient had a history of CML treated with imatinib for 4 years, with loss of complete hematological response for 3 months before being diagnosed with RCC and lung metastases. Due to a T315I mutation in the BCR-ABL1 gene, the treatment regimen included a novel combination of Axitinib, Dasatinib, and low-dose nivolumab. The patient showed a remarkable therapeutic response with a complete metabolic response accompanied by a highly significant reduction in the size of the tumor and complete resolution of the metastatic lung lesions, as well as a major molecular response in terms of CML disease control.