Triple Negative Breast Cancer

P1, N=60, Recruiting, Immunomic Therapeutics, Inc.

The nomogram based on HER2 status shows promising preliminary predictive performance in predicting pCR. Given the lack of external validation and single‑center design, this model remains exploratory and hypothesis‑generating.

SPDEF is specifically downregulated in TNBC, and its high expression is associated with earlier tumor stage and favorable clinical outcomes. SPDEF suppresses TNBC cell proliferation, migration, and invasion while promoting apoptosis through modulation of apoptosis-related protein expression, highlighting its potential as a prognostic biomarker and therapeutic target for TNBC.

NRF2 directly binds to and transcriptionally activates CARM1, thereby enhancing ferroptosis resistance and promoting TNBC progression. These findings reveal a novel molecular mechanism underlying TNBC malignancy and suggest that targeting the NRF2-CARM1 axis, particularly in combination with ferroptosis inducers, may provide a potential strategy for TNBC treatment.

Molecular docking studies at the STAT3-SH2 domain corroborated the biological data, confirming that the flexibility of the thioether linkage in the 5a and 5b provided optimal binding energies compared to the more rigid or bulkier inactive analogs. This newly accessible imidazole class successfully establishes dual STAT3/NF-κB inhibition with direct antimetastatic efficacy, positioning 5b as a highly promising TNBC lead warranting further in vivo validation and clinical translation.

Mechanistically, 5i increases DNA damage by inhibiting SYK-mediated CtIP phosphorylation and shows synergy with the PARP inhibitor Olaparib. These findings establish 5i as a promising therapeutic candidate and demonstrate the potential of SYK inhibition as a strategy to overcome HR-mediated resistance in TNBC.

TNBC cell-derived exosomal circ_0005397 drives M2 macrophage polarization via the miR-204-5p/STAT6 ceRNA network, consequently reshaping the tumor immune microenvironment and accelerating TNBC progression. This axis may serve as a promising candidate for TNBC early diagnosis and a potential target for immunotherapy-based interventions.

We found that RNA-binding protein RBM38 is correlated with exon 4 inclusion, and RBM38 knockdown further sensitized BRCA1-mutant cells to MEK1 inhibition. Together, these findings define an RBM38-HORMAD1 signaling as a potential therapeutic vulnerability in BRCA1-mutant breast cancer and suggest that targeting splicing regulation may represent a promising strategy to enhance treatment efficacy.

Classified TNBC cases showed clinicopathologic and ultrasonographic heterogeneity. DeepLabV3+ and nnU-Net showed numerically favorable segmentation performance in this exploratory fixed-split cohort and may be considered candidate region-of-interest (ROI)-generation approaches, pending validation in larger independent datasets.

Collectively, these findings establish HER2‑low expression as a negative predictor of immunotherapy response, shaped by a less immunogenic tumor microenvironment. These results provide important insights into the distinct immunological features of HER2‑low triple‑negative breast cancer and warrant further mechanistic and clinical investigations.

These TNBC cells were significantly more sensitive to cisplatin than wild-type TNBC cells, consistent with our clinical data. In conclusion, RAD51D-deficient tumors were shown to have a phenotype similar to that of BRCA1-deficient tumors, and further investigation of responses to DNA-damaging agents, particularly platinum-based chemotherapy, is warranted.

P1, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial completion date: Apr 2026 --> Apr 2029 | Trial primary completion date: Apr 2026 --> Apr 2028