Treatment of HER2+ mBC with and without BMs in Saudi Arabia largely aligned with international recommendations identified in our literature analysis, although access to lapatinib, tucatinib and neratinib can be limited and may lead to use of alternative regimens. The tucatinib-combination may be considered the standard of care for adult patients with HER2+ locally advanced or mBC who have received at least two prior anti-HER2+ treatment regimens, including patients with BMs. Ensuring access to innovative HER2+ mBC therapies across Saudi Arabia is crucial to supporting best practice.
Patients in the high‑risk group showed improved responses to lapatinib, BI‑2536, OSI‑027, and SB505124, whereas those in the low‑risk subgroup had better sensitivity to axitinib, epirubicin, fulvestrant, and olaparib. Additionally, CD24 overexpression in BC cell lines promoted proliferation and migration, and inhibited apoptosis. These findings contribute to personalized treatment strategies and help elucidate the tumor microenvironment characteristics of BC patients.
9 days ago
Journal • PARP Biomarker
|
CD24 (CD24 Molecule) • BCL2A1 (BCL2 Related Protein A1) • CREB3L1 (CAMP Responsive Element Binding Protein 3 Like 1) • CRIP1 (Cysteine Rich Protein 1) • SFRP1 (Secreted frizzled related protein 1) • XBP1 (X-box-binding protein 1) • AIF1 (Allograft Inflammatory Factor 1) • NKX3-1 (NK3 homeobox 1)
In the context of the Chinese health system, none of the three alternative regimens-pyrotinib plus capecitabine, T-DM1, and T-DXd-demonstrated cost-effectiveness relative to lapatinib plus capecitabine at the current WTP threshold.
Among the tested analogs, 6e, 6f, and 6 g exerted promising cytotoxicity toward HS 578 T cells where compound 6f exhibited significant antiproliferative activity with an IC50 of 3.06 µM, exceeding that of Lapatinib by 7.6 fold...The findings illustrated that analog 6f exerted the most potent CDK-2 inhibition with an IC50 equal to 0.277 µM, which is approximately threefold the activity of Roscovitine (0.833 µM). As well, compound 6f arrested HS 578 T cell cycle at both S and G2/M phases and stimulated apoptosis by increasing Bax and Caspase-3 expression with a concurrent decline in the expression of Bcl-2. Additionally, ADMET prediction and the binding interaction of the most active derivatives with CDK-2 have been studied in silico to evaluate their potential as important antitumor agents.
Therapeutic limitations of current targeted therapies include resistance, toxicity, and the modest efficacy of monotherapies. As such, future investigations must refine endpoints (e.g., hearing stabilization vs. tumor regression), optimize dosing strategies, and personalize therapy based on age, tumor biology, and clinical trajectory. This review highlights the translational challenges and opportunities that lie ahead in delivering clinically efficacious therapies specific to each patient.
VS biology reflects integrated genetic and epigenomic dysregulation. Advancing care will require multi-omic classification, biomarker-driven trials, and combination therapies targeting both signaling and epigenetic vulnerabilities. Future management is expected to shift toward personalized, mechanism-based strategies aimed at durable tumor control while preserving hearing and quality of life.
Consistent with these subtype-specific features, CS1 tumors exhibited distinct sensitivities to dasatinib, lapatinib, paclitaxel, and cisplatin, indicating immune-state-associated therapeutic vulnerabilities. Together, these findings suggest a RUNX1-associated immunosuppressive tumor ecology in UVM and provide a conceptual framework for immune-state-guided therapeutic strategies.
1 month ago
Journal
|
RUNX1 (RUNX Family Transcription Factor 1) • BAP1 (BRCA1 Associated Protein 1)
In further support, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, attenuated mitochondrial respiration in NF639 murine mammary tumor epithelial cells. Together, this data highlights that the typical correlation between mitochondrial content and respiratory capacity may not apply to all tumor types and implicates HER2-linked activation of mitochondrial respiration supporting tumorigenesis in this model.
These results indicate a synergistic interaction between tras tuzumab and blood serum in both groups. We also found significant differences in CI values between healthy donors and breast cancer patients: blood serum samples from patients enhance the effect of trastuzumab to a greater extent.
All patients received anti-HER2 TKI therapy (including pyrotinib and lapatinib) in 28-day cycles. No unexpected toxic effects were reported. After progression following TKI therapy, T-DXd exhibited notable antitumor activity, although no significant efficacy differences were observed among ADC, mAb, and TKI groups.