Triple Negative Breast Cancer

We concluded that CV extract modifies the tumour microenvironment and changes macrophage polarisation toward functioning as an anti-tumour agent. Therefore, it is promising to use in the treatment of TNBC-associated macrophages.

We observed significant positive patient-level correlations between DFS and OS, IDFS and OS, and DDFS and OS in early-stage HER2- BC. Our IDFS and DDFS findings advance the understanding of the role of these DFS endpoints as predictors of OS, and their potential utility as surrogate endpoints in clinical trials of early-stage HER2- BC, given additional validation in trial-level meta-analyses.

Furthermore, we identified distinct miRNA expression patterns for the major intrinsic subtypes of breast cancer, specifically luminal A, luminal B, HER2-enriched, and triple-negative breast cancer. This experimental approach specifically validates miRNA sequencing as a technique for breast cancer detection in urine samples and opens the door to a new, easy, and painless procedure for different breast cancer-related medical procedures such as screening but also treatment monitoring.

Furthermore, ATP6V0D2 knockdown inhibited TNBC cells invasion, migration, and proliferation abilities. ATP6V0D2 acts as a promising indicator for both diagnosis and prediction of outcomes in breast cancer and could potentially be a novel therapeutic target for BRCA.

Additionally, patients with HER2 and TN primary breast tumors exhibited the shortest DFS. Based on these findings, the study recommends the implementation of biomarker testing for recurrent breast cancers as a valuable strategy to inform and guide decisions regarding the selection of rescue chemotherapy, endocrine therapy, and targeted therapy.

Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via hRS7, the antibody component of Sacituzumab govitecan (SG), enhances the anti-PD1 response associated with improved T cell accessibility and effector function...This study defines a new mechanism of barrier-mediated immune exclusion in cancer controlled by TROP2-dependent tight junctions. This mechanism drives tumor progression but can be targeted via TROP2-directed antibody drug conjugates to activate anti-tumor immunity and enhance immunotherapy response.

MBC-005 did not induce off-target toxicity; and, as such, would be amenable to multiple rounds of administration. Nevertheless, it is notable that the positive effects of MBC-005 treatment on increasing survival and decreasing tumor volume in mice was achieved using a single dose.

These systems have good prospects in improving the bioavailability of PTX, enhancing tumor targeting, reducing toxicity, controlling drug release, and reverse tumor multidrug resistance (MDR). This review provides valuable insights into the clinical development and application of PTX-targeted NDDS in the treatment of TNBC.

Moreover, cephaibol A significantly inhibited tumor growth and improved survival rates in the MDA-MB-231 cell mice model. These findings established cephaibol A as a potential antitumor agent that inhibited tumor cell proliferation in vitro and in vivo by affecting mitochondrial dysfunction and inducing apoptosis in MDA-MB-231 cells through structural damage.

The results demonstrate that this test can accurately quantitate the level of promoter methylation at the BRCA1 and RAD51C genes using FFPE samples, even when the extracted DNA is extremely degraded or the input amount is limited. This test increases the precision of diagnostic tests aimed at identifying patients who are likely and unlikely to respond to PARP inhibitor therapy.

These findings suggest that of HA-Se@CPT, Met, and GW280264X may inhibit tumor progression in BC by improving the function and infiltration of CD8+ T cells. Their effect is more pronounced when used in combination.

We delve into the specifics of PARPi, androgen receptor (AR) inhibitors, Cancer stem cells (CSCs), PI3K/ Protein Kinase B (AKT)/ mammalian target of rapamycin (mTOR), the transforming growth factor-beta (TGF-β), Ntoch, Wnt/β-catenin, hedgehog (Hh) pathway inhibitors, Epigenetic target-mediated drug delivery, ADCs, immune checkpoint inhibitors (ICIs)and novel immunotherapeutic solutions, contextualizing TNBC within current treatment paradigms. By elucidating the mechanisms of these drugs and their prospective clinical applications, we aim to shed light on the challenges and underscore the beacon of hope that translational research and innovative therapies represent for the oncology field.

P1/2, N=607, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=425 --> 607

P2, N=60, Not yet recruiting, Sun Yat-sen University

This research is corroborated by an in-house cohort showing lower survival rates in TNBC patients with higher cholesterol production gene activity. This suggests a new treatment approach for TNBC by simultaneously targeting CDK4/6 and CDK7, warranting additional clinical trials.

Our results suggest that TRPS1 IHC represents a highly accurate and reliable method for differentiating metastatic BC from PAC.

Breast cancer patients with TTK, TOP2A, CENPF, and CCNA2 upregulation had a poor prognosis; TTK and CCNA2 were partially disordered, whereas TOP2A and CENPF were primarily disordered, according to IDR analysis. According to our study, TOP2A and CENPF may be useful therapeutic targets for disruption of the TNBC PPI network.

About 20% of interval cancers were evident on screening mammograms. The most common radiologic finding in interval cancers was asymmetry/mass. Interval cancers are diagnosed at a more advanced stage than cancers identified at screening, so they sre more often treated by mastectomy. Reviewing interval cancers is essential for quality control in screening programs.

Mechanistically, intracellular CD28 directly bound to Cd274 mRNA and recruited spliceosomal factor SNRPB2 to stabilize Cd274 mRNA in nucleus, promoting PD-L1 expression and immune escape. Therefore, disrupting cancer cell CD28-mediated immune escape may provide a potential approach to improve breast cancer immunotherapy.

This review highlights the therapeutic approaches, and the challenges encountered in targeting EGFR-specific mutations. It suggests the need to develop more advanced higher-generation inhibitors for use in combinatorial therapy along with chemo-or-immune therapeutics in clinics as a breast cancer treatment strategy against relapse of the disease.

circUBR5 knockdown facilitated miR-340-5p-targeted CMTM6 via a ceRNA mechanism, thereby reducing c-MYC-mediated ribosome biogenesis and accelerating chemosensitization of DTX-resistant TNBC cells, which offered a theoretical guideline for clinical research on the feasibility of inhibiting ribosome biogenesis to reduce TNBC chemoresistance.

43 could inhibit the proliferation, migration, and glycolysis, induced mitochondrial membrane potential decreased and apoptosis in BT-549 and MDA-MB-231 cells. Collectively, these results demonstrate that 43 is a potent SIRT3 activator with the potential to anti-TNBC through signaling pathways regulated by SIRT3.

These cyclin-dependent kinase (CDK)12/CDK13, CDK7, and phosphoinositide 3-kinase inhibitors, respectively, decreased metabolic activity in TNBC cell lines and promote a gene expression profile consistent with the reversal of the epithelial-to-mesenchymal transition, indicating these kinase networks potentially mediate metastatic behavior. These data identified novel kinase targets and kinase signaling pathways that drive metastasis in TNBC.

P2, N=333, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

P2, N=80, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2024 --> Dec 2025

We then detected the epithelial-mesenchymal transition (EMT) markers [i.e., epithelial cadherin (E-cadherin), matrix metallopeptidase 9 (MMP9), vimentin, and snail family transcriptional repressor 1 (SNAIL)], phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK), to identify the potential mechanisms of AKF-PD. AKF-PD not only mitigates CP-induced AKI but also enhances the anti-cancer efficacy of CP. Our findings provide valuable insights into the treatment of NSCLC and may have clinical applications.

The best strategy to detect all PVs was an MS ≥3 with specificity of 32.6%. In order to detect higher PV rates on a population basis the best strategy is to reduce the MS threshold for genetic testing.

P2, N=129, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P3, N=504, Not yet recruiting, Shanghai Escugen Biotechnology Co., Ltd

P2, N=19, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Oct 2026 --> Feb 2027

P1, N=196, Recruiting, Nanjing Immunophage Biotech Co., Ltd | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.

Knockout of the endogenous STT3 isoform in TNBC cells partially reduced the glycosylation status of CD24. Our results demonstrate the critical role of N-glycosylation of CD24 in weakening drug sensitivity by inhibiting ferroptosis, highlighting new insights that targeting N-glycosylation of CD24 has great potential to promote chemotherapy sensitivity and efficacy.

Additionally, diminished TSNAX-DISC1 and CYP1B1 expression similarly restrained cell proliferation, potentially by reducing Wnt/β-catenin signaling. These findings may represent a novel therapeutic approach for patients with radioresistant triple-negative breast cancer.

Young patients with breast cancer have a lower 5-year survival than the UK average for all ages, and patients in this single-centre study with ER+ tumours appeared to have better short-term but similar longer-term outcomes compared to ER- breast cancer.

Remarkably, we identified a prognostic signature comprising 40 significant genes in the MHC-II-expressing tumors in which machine leaning models with the signature successfully predicted patient survival outcomes and the degree of immune infiltration. This study advances our understanding of the immunological basis of cancer progression and suggests promising new directions for therapeutic strategies.

P2, N=40, Not yet recruiting, Fudan University

P1, N=230, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Feb 2025 --> Jun 2025

Currently, there are no predictive tools available to determine organ-specific cancer risk in MINAS patients. Given the uncertainty in predicting the phenotypic effect of multiple variants in CSGs, ongoing clinical surveillance and sharing data from complex cases are crucial for improving risk stratification in this condition.

P3, N=254, Active, not recruiting, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Trial completion date: Dec 2024 --> Mar 2025

P2, N=106, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed

P2, N=20, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2025