Triple Negative Breast Cancer

P2, N=416, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Based on multi-omics analysis, our findings indicate that the PI3K/AKT pathway is a key factor contributing to the significant prognostic disparity between TNBC and Non-TNBC. Within this pathway, the MYB gene emerges as a potential therapeutic target. This discovery provides a potential basis for future research exploring MYB as a therapeutic target for TNBC patients.

Functional validation using actinomycin D and cycloheximide treatments demonstrated that compound 2 suppresses RPL27A and RPLP0 expression at the translational level, thereby inhibiting tumor cell invasion and migration and exerting robust antitumor effects. Collectively, these findings provide novel insights into the anticancer mechanisms of EEF1A1-targeting agents and highlight EEF1A1 as a promising therapeutic target for the treatment of TNBC.

Functional mechanistic studies with various biophysical experiments revealed the compound's pronounced effect in apoptosis induction and biological function interference, such as Bax upregulation, caspase-3/PARP cleavage, and AKT suppression, mitochondrial membrane potential disruption, accumulation of cytoplasmic and mitochondrial ROS, which led to sub-G0 accumulation and G2/M phase cell cycle arrest. Structure-activity and cheminformatics analyses provides identification of potential key pharmacophoric features and favorable natural product- and drug-likeness profiles.

Furthermore, PRR5 abundance was particularly enriched and correlated with that of phosphorylated ERK in samples from patients with TNBC. Our results highlight cross-talk between mTORC2 and ERK signaling downstream of LINC01133 and PRR5 that may be therapeutically targeted to treat TNBC.

P1, N=149, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting | Trial completion date: May 2028 --> Feb 2028

Overall, Genipin, a gut microbiota-activated metabolite and a key component of XHP, suppresses TNBC angiogenesis by targeting the HIF-1α/HSPG2 pathway. These findings provide mechanistic insights into the therapeutic potential of XHP and highlight Genipin as a promising candidate for antiangiogenic therapy in TNBC.

Longer OS and DFS were associated with non-White race, lower stage and grade, negative LVI, and higher ER/PR levels. These findings confirm HER2-low status is common but not independently prognostic for response or survival.

During the study period, the overall survival rate in this cohort of women with breast cancer was 83.1% at five years and 65.5% at ten years. Different clinical, biological and tumor-related factors significantly affected prognosis in this population.

TMEPAI appears to facilitate paclitaxel resistance in triple-negative breast cancer cells by promoting cell survival signaling, inhibiting apoptosis, enhancing drug efflux, and initiating epithelial-mesenchymal transition (EMT). Targeting TMEPAI may be a viable approach to overcoming resistance and improving treatment outcomes in triple-negative breast cancer cells.

This strategy integrates sonodynamic therapy (SDT) with localized immune activation, addressing challenges of instability and inefficient delivery. The platform thus offers a precise and effective approach to stimulate antitumor immunity and enhance therapeutic outcomes for TNBC where no tumor targeted therapy is currently available.