Breast Cancer

In conclusion, the FXR was first reported as a tumor promoter that enhanced the proliferation and metastasis of breast cancer cells through regulating CBP-dependent p53 K382 acetylation. It proposes that FXR may serve as a potential therapeutic target for the treatment of breast cancer.

In addition, we have presented four enhancer reprogramming mechanisms (transcription factor cooperation, pioneer factor binding, dynamic assisted loading, and tethering) and the multiple enhancer-promoter contact models. Based on these mechanisms and models, this review proposes that the combination of multiple therapy strategies such as agonists/antagonists of SHRs plus endocrine therapy and the adoption of the latest sequencing technologies are expected to improve the efficacy of ER positive breast cancer treatment.

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.

HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.

According to literature, and TailorX trial data, our study confirms the importance of ODX as a tool able to guide therapeutic choices and ensure patients the most appropriate adjuvant treatment.

Longitudinal multimodal DL can be useful in predicting pCR. The stacking model can be used as a new tool for the early noninvasive prediction of the response to NAC, as evidenced by its excellent performance, and therefore aid the development of personalized treatment strategies for patients with breast cancer.

Our study revealed novel functions of DLL4 in cell stemness and immune infiltration, including NET formation and T cell exclusion, which collectively contributed to THP neoadjuvant therapy resistance in HER2+ BC. Furthermore, we provided a CAR-T-based therapy to sensitize the THP neoadjuvant therapy.

Combined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab.

Molecular docking studies revealed that selected protein targets strongly interact with bioactive compounds, and the estimated inhibition constants (Ki) of JAK2, STAT3, COX-2, HPV31 E6, EGFR1, TP53, and PARP1 were significantly decreased compared to acetylsalicylic acid. This could be a clear indication that these protein targets are implicated with antiproliferative efficacy, thereby warranting the potential of (1) and (7) to be used as anti-breast cancer drug candidates.

The gene expression analysis confirmed the decrease in the expression of anti-inflammatory genes, such as cox-2 and nf-κb, and apoptosis inhibitor genes, such as bcl-2 and mdm2. By regulating the anti-inflammatory and apoptosis inhibitor genes, FA-CS-DP nanoparticle prevents neoplastic growth in the zebrafish model.

Moreover, we found that VIF-mediated nuclear dysmorphia led to defects in DNA repair. Together, our results unveil a novel role of VIFs in cancer cell nuclear dysmorphia, which is associated with genome instability.

Comparative analysis of secreted cytokine profiles in THP-1 M1 macrophages exposed to either CTRP8, relaxin-2 (RLN2), or the small molecule RXFP1 agonist ML-290 revealed ligand-specific cytokine signatures. Our study identified novel subsets of CTRP8 + myeloid derived innate immune cells and links this adipokine to pro-inflammatory events in the TME of BC.

Finally, studies in Caenorhabditis elegans evidenced the safety of FA-NLC-RAP characterized by a complete absence of toxicity in this animal model. Therefore, the findings imply that FA-NLC-RAP holds considerable promise for the treatment of breast cancer.

In contrast, both MS105 and PTK6 kinase inhibitor effectively inhibit breast cancer cell migration, supporting the differing kinase dependencies of PTK6's oncogenic functions. Our studies support PTK6 degraders as a preferred approach to targeting PTK6 in cancer.

This was accompanied by reduced expression of AKT1 and ABCB1 genes, reinforcing the anticancer efficacy of PD/SOF combination therapy. In conclusion, the findings suggest that PD/SOF could serve as a promising anticancer treatment strategy, warranting further investigation for potential clinical applications and mechanistic studies in vivo.

Metformin (MET), a commonly used oral drug for type 2 diabetes, has played a vital role in fostering an immunostimulatory environment...Based on the function of MET, there is a marked increase in the infiltration of activated CD8+ T cells and NK cells, which subsequently augments ferroptosis to a greater extent. Taken together, Fe-PDA-MET NPs activate a ferroptotic positive-feedback loop for effectively control TNBC progression, which offers a promising therapeutic modality to enhance the immunogenicity and reshape the TIME.

FOXD1 activates the glycolysis pathway by upregulating KIFC1, thereby facilitating BC cells' DDP resistance. Therefore, the FOXD1/KIFC1 axis linked the glycolysis pathway to DDP resistance and may be a promising new target for reinforcing DDP resistance in BC.

These results highlight the aptasensor's high sensitivity, specificity, and potential for real-time, non-invasive EGFR monitoring in clinical samples such as serum, sweat, and saliva. This approach would facilitate early detection of cancer and personalized diagnostics in point-of-care settings.

The 2%, 3% and 4% formulations presented IC50 values of 14.7, 26.2 and 47 μg/ml, respectively, with complete destruction of MCF-7 spheroids. Elevated TNF-α levels suggested an inflammatory-mediated mechanism of action. 2% Zingiber officinale-derived ZnO NPs showed antitumor potential against deserving further mechanistic and in vivo explorations.

The MNAzyme biosensor exhibited a low detection limit of 0.02 ng mL-1 and excellent selectivity. Furthermore, the proposed biosensor can also change the recognition element by changing the aptamer sequence to detect various biomarkers, holding great potential for cancer diagnosis and other related biomedical applications.

The CAM assay analysis has demonstrated that knocking out the PI3Kca gene and radiotherapy substantially reduced the total vessel network length and the number of junctions. The findings of our investigation indicate that the integration of radiation therapy with PI3Kca yielded enhanced radiosensitivity, leading to a marked retardation of tumor progression and an increased survival rate.

Fourteen different articles showed that the use of cytokines and cancer vaccines revealed new possibilities to treat breast cancer with antibodies against PD-1/PD-L1 (pembrolizumab), PI3K/Akt/mTOR (alpelisib and everolimus), CAR T-cell (chimeric antigen receptor), PARP (poly ADP-ribose polymerase), and CTLA4 (cytotoxic T-lymphocyte-associated protein 4), and with representative relevance of changing in tumor microenvironment. Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) targets show also a high effectivity. In recent years, the release of new strategies has become promising, for changing the microenvironment and de-escalation of therapy based on tumor biology, novel biomarkers, and tumor spread.

We achieved a remarkable response in the metastatic lesions with minor toxicity issues. This case highlights the importance of utilizing up-to-date therapeutic agents and reactive decision-making during personalized cancer treatment.

Consequently, SIGLEC15 correlates with tumor immune infiltration, molecular subtypes, and BRCA progression and prognosis. However, further research is required to elucidate the role of SIGLEC15 in breast cancer.

A higher rate of P/LP variants is seen among Emirati patients at risk for hereditary breast and ovarian cancer syndrome compared with reports of similar patients from Western populations. Efforts to increase utilization and awareness of germline genetic testing are warranted among Emirati patients.

Baseline CRP, NLR, BMI level, and marital status are significant predictors of CIPN occurrence throughout chemotherapy. Our CART model was better at ruling out individuals who would not experience CIPN. The CART model may provide insight into the future development of individualized patient care and prevention strategies.

This INFLUENCE 3.0 models showed moderate performance in LRR and CBC prediction. The models have been made available as online tool to enable clinical decision support regarding personalised follow-up.

In this study, we demonstrate that TRIM50 is downregulated in human breast cancer and that its overexpression closely correlates with diminished invasion capacity in breast cancer, suggesting that TRIM50 may serve as a diagnostic marker and therapeutic target. TRIM50 plays a key role in breast cancer proliferation and potentially serves as a prognostic and therapeutic target.

Des-[Arg9]-Leu8-BK and HOE-140 were used as antagonists for the B1 and B2 receptors...Moreover, the migration and invasion induced by kinins in breast cancer cells were inhibited when focal adhesion kinase (FAK) and Src inhibitors were used. The novelty revealed in our work is that B1 and B2 receptors activated by LDBK and BK induce migration and invasion in breast cancer cells via a mechanism that involves the FAK-Src signaling pathway, and the antagonism of both receptors in vivo impairs breast tumor growth.

Based on the current literature, PSMA-targeted PET/CT cannot be suggested as a diagnostic tool to assess BC extent in any clinical scenario. However, based on the PSMA expression observed in triple-negative patients, it can be proposed as a tool to evaluate whether BC patients could benefit from PSMA-targeting radioligand therapy.

Yet emerging clinical and experimental evidence points to progestogens (endogenous progesterone or synthetic progesterone [progestin]) as the primary hormonal driver underlying seemingly estrogen-associated breast cancer risk...Estrogen HRT has shown an array of proven benefits, including ameliorating menopausal symptoms and improving bone health. Collective evidence thus suggests that estrogen HRT is likely to offer health benefits to perimenopausal or postmenopausal women, including breast cancer survivors, as well as young BRCA1/2 carriers with prophylactic oophorectomy for ovarian cancer prevention.

Our results indicate that adenocarcinomas of intestinal-type, in distal vagina or vestibular vulva, might be a unique and single entity, probably originating from cloacogenic embryonic remnants and/or ectopic colorectal mucosae inclusions. An open question would be to explore the efficacy of systemic drugs prescribed in colorectal cancers, in VVAIts.

Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.

Physicians should make additional efforts to evaluate age-specific treatment efficacy and treatment-induced toxicities. Further efforts to enhance the representation of older patients in breast cancer trials are warranted.

Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

Lastly, depletion of FOSL1 inhibits tumor spheroid growth and stemness properties of TNBC cells. Taken together, these findings uncover the key epigenetic role of FOSL1 and highlight the potential of targeting the FOSL1-TCOF1 axis for TNBC treatment.

HER2 and other tumor-associated antigens have served as valuable benchmarks for developing novel therapies, such as antibody engagers and CAR T-cells. However, further research is essential to identify and validate new target antigens that can enhance therapeutic efficacy and broaden the clinical applicability of these approaches.

Importantly, 10h induced immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation, and activated T cells, thereby initiating antitumor immunity. In conclusion, compound 10h is a novel dual-target ROCK/HDAC inhibitor that represents a promising treatment strategy for TNBC.

Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.

There were significant differences between the CR and ML models in predicting LVI status. Our study demonstrated that the machine learning models exhibited superior performance in predicting LVI status based on pretreatment MRI compared to the CR model, which does not necessarily rely on a priori knowledge of visual morphology.

IDO1 promoter methylation and expression are associated with prognosis, immune cell infiltration, immune-related pathways, and immunomodulator expression in breast cancer. Our findings provide evidence for the validation of IDO1 promoter methylation as a promising biomarker to predict responses to immune checkpoint inhibitors in patients with breast cancer.