BCR (BCR Activator Of RhoGEF And GTPase)

5-fluorouracil and VEGF (vascular endothelial growth factor) inhibitors are the agents most commonly linked to abnormal vasoreactivity, whereas BCR-ABL (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog) inhibitors and immune checkpoint inhibitors have been associated with accelerated atherosclerosis...Key contributors include endothelial injury and dysfunction, oxidative stress, and inflammation. An understanding of the mechanisms of vascular toxicities may facilitate optimal treatment and preventive strategies in patients with cancer.

The visual and texture features of the Siamese architecture help in the capture of molecular similarities based on electrostatic and non-covalent interaction profiles. Therefore, the developed protocol offers a suitable approach in computational drug discovery, being a promising framework for virtual screening, drug repositioning, and the identification of novel therapeutic candidates.

However, the toxicity and resistance associated with the use of imatinib, a first-generation Bcr-Abl inhibitor, in cases where the T315I mutation exists, necessitates the need for new tyrosine kinase inhibitors...However, investigating different combined scaffolds enhances the chance of successfully developing novel drug candidates. Overall, the information provided in this review can be beneficial to researchers with an interest in chronic myeloid leukemia and tyrosine kinase inhibitors.

These findings underscore the necessity for vigilant, protocol-driven monitoring of blood counts and cardiac function (including echocardiography) during dasatinib therapy. Proactive management strategies should be considered to mitigate these risks and improve treatment safety.

At present, there is no established consensus on the treatment of Ph + MPAL, and reports on cases with the atypical e13a3 BCR::ABL1 fusion are particularly scarce. This finding will bring new insights and references for the diagnosis and treatment of Ph + MPAL.

The treatment safety of the entire process was excellent. In summary, olverembatinib provides more treatment options for rare diseases such as 8p11 myeloproliferative syndrome.

This WES-AI-ML framework provides mutation-guided therapies for BC-CML, enabling real-time stratification and Food and Drug Administration-approved drug repurposing. While this exploratory study is limited by its small sample size (n = 7), it establishes a methodological framework for precision oncology stratification that warrants validation in larger, multi-center cohorts.

In conclusion, MSI2 inhibition, in combination with TKI therapy, has shown to overcome drug resistance and mitigate senescence in preclinical CML models, and suggesting a potential strategy to target CML LSCs.

By conjugating the BCR-ABL inhibitor dasatinib with the LC3B-binding ligand GW5074, we engineered eight distinct ATTEC variants with diverse linkers...The activity of DS-PPE-GW was further enhanced by the autophagy activator rapamycin, confirming its autophagy dependence. Notably, DS-PPE-GW did not increase global autophagic flux, suggesting selective engagement of pre-existing autophagosomes. These findings demonstrate that strategically designed ATTECs can efficiently degrade BCR-ABL, targeting both its catalytic and non-catalytic functions, and provide a promising strategy for next-generation CML therapy.

Maslinic acid (MA), a plant-derived pentacyclic triterpene, was compared to the FDA-approved drugs dasatinib (DAS) and doxorubicin (DOX) to determine its antileukemic potential. Thus, these results illustrate that MA may act as a natural scaffold with antileukemic properties and call for additional experimental confirmation. The online version contains supplementary material available at 10.1007/s40203-025-00478-3.

P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2025 --> Oct 2026

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