HER-2 (Human epidermal growth factor receptor 2)

This extensive data pool suggests significant benefit of CDK4/6i regimens after disease progression as compared with ET monotherapy. Our data also support current guideline recommendations of ET-based therapies over chemotherapy for treatment sequencing.

P1/2, N=46, Terminated, Henan Cancer Hospital | Trial completion date: Jan 2026 --> Jul 2024 | Active, not recruiting --> Terminated; Investigators' decision

P2/3, N=849, Active, not recruiting, Immutep S.A.S. | Recruiting --> Active, not recruiting

In hormone receptor-positive, HER2-negative breast cancers, a growing number of revolutionized personalized therapies are in clinical use or on trials, such as CDK4/6 inhibitors and immune checkpoint inhibitors in adjuvant and neoadjuvant settings, and PIK3CA inhibitors in metastatic disease. In this review, we focus on biomarkers associated with those new therapeutic targets and molecular applications for genetic alterations associated with drug resistance or interaction from a pathology perspective for selecting and optimizing breast cancer treatment.

Five-profile classification provides a more accurate idea about the rate of potential change in treating BC in the metastatic setting.

Our study showed differences between in situ and invasive biomarker expression. According to our findings, owing to heterogeneity, in situ components can't be representative of invasive components for treatment choices.

Significant cardiovascular signals were identified for 17 TKIs, including erlotinib, gefitinib, and imatinib...Heatmaps indicated significant signals for drugs such as lapatinib in males and gefitinib in younger patients...These results underscore the importance of individualized risk assessment and management of TKI-treated patients. In conclusion, this study provides valuable insights into the cardiotoxic risk of TKIs, which is essential for developing tailored treatment plans.

Today, novel agents called antibody drug conjugates (ADCs), including enfortumab vedotin (EV) and sacituzumab govitecan (SG), have been approved for la/mUC offering patients treatment options following or instead of traditional chemotherapy...In 2023, EV in combination with pembrolizumab almost doubled progression-free and overall survival versus platinum-based chemotherapy, which led to accelerated FDA approval as first-line treatment for all patients with la/mUC...Finally, a recent cancer agnostic accelerated approval for trastuzumab deruxtecan (T-DXd) in HER2-positive (IHC3+) solid tumors provides another active ADC option for biomarker-selected patients with treatment refractory la/mUC. Several new ADCs are being investigated in urothelial cancer (UC) clinical trials. This review summarizes the clinical studies and real-world data regarding the use of ADCs in UC.

NDRG1 protein expression is statistically significantly associated with regional metastasis of breast cancer (p=0.015). The differences were due to a higher frequency of cases with NDRG1 positive versus negative status in the group of breast cancer with lymph node metastases.

CT-defined low SMD predicts poor treatment outcomes in patients with ABC undergoing first-line treatment with aromatase inhibitors and CDK4/6i.

By analyzing clinical evidence, commercial presence, reimbursement mechanisms, guideline recommendations, regulatory pathways, and local experiences, this study reveals the complex factors that influence the adoption of personalized medicine technologies. By highlighting these challenges, this article offers valuable insights into strategies to facilitate the integration of innovative diagnostic tools into clinical practice across Europe, ultimately leading to improved treatment decision-making for cancer patients.

This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.

Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer's current diagnostics and treatment modalities.

Baseline ESR1 mutations in EV-DNA were associated with shorter progression-free survival (PFS) across the cohort, with the Y537S mutation showing a particularly strong impact on the outcome of fulvestrant-treated patients. In contrast, PIK3CA mutations in EV-DNA did not significantly correlate with PFS, whereas in ctDNA, they were linked to poor outcomes. Altogether, this study positions EV-DNA as a valuable biomarker alongside ctDNA, enriching the understanding of different analytes in liquid biopsy and supporting strategies for HR+/HER2-mBC in precision oncology.

We visualized these interactions using Cytoscape to generate individual and combined drug-gene networks, focusing on frequently used drugs such as Erlotinib, Gefitinib, Lapatinib, and Cetuximab...Combined drug networks, such as those for Cetuximab with Lapatinib, Cetuximab with Erlotinib, and Erlotinib with Lapatinib, revealed potential synergies that could enhance therapeutic efficacy by simultaneously influencing multiple genes and pathways. Our findings suggest that a network-based approach to analyzing drug combinations provides valuable insights into the molecular mechanisms of HER2+ breast cancer and offers promising strategies for overcoming drug resistance and improving treatment outcomes.

In conclusion, PD-L1 expression in TNBC shows significant discordance post-treatment, highlighting the need for routine testing and further research on predictive biomarkers.

T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required.

Four chemotherapy agents were chosen as priority hits for mechanistic follow-up due to their ability to enhance T-cell-mediated cytotoxicity at multiple doses and multiple time points: paclitaxel, bleomycin sulfate, ispinesib, and etoposide. Based on the ability to increase tumor cell susceptibility to T-cell-mediated cytotoxicity while minimizing T-cell toxicity, bleomycin was identified as the most promising lead candidate. Overall, the results of these studies provide mechanistic insight into potential new chemotherapy partners to enhance anti-PD-1 efficacy in TNBC patients.

The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies.

Pep-7 emerged as the most promising therapeutic peptide, displaying strong binding stability, favorable binding free energy, and molecular stability in HER2-overexpressing cancer models. These findings suggest pep-7 as a viable therapeutic candidate for HER2-positive cancers, offering a potential novel treatment strategy against HER2-driven malignancies.

This integrative approach unveils a complex landscape of HER2 drug resistance in breast cancer, identifying crucial miRNAs, target genes, and significant pathways. The findings offer novel insights into the mechanisms governing drug resistance and highlight the potential for enhancing therapeutic strategies. Future studies are necessary for experimental validation to further explore the complex mechanisms involved.

Synthesizing evidence from diverse studies, this review provides insights into the prognostic and predictive landscape of CRC, highlighting the potential clinical implications of identified determinants. Understanding the multifaceted nature of prognostic and predictive factors in CRC is imperative for the advancement of personalized treatment strategies and improvement of patient outcomes.

This study highlights the strengths and limitations of amplicon-based NGS assays in detecting amplifications using real-world data.

The multi-parametric MRI model we developed outperformed the base models in predicting breast cancer molecular subtypes. Our study also showed the potential of FS-T1WI base model in predicting breast cancer molecular subtypes.

Although male breast cancer makes up less than 1% of all breast cancers, its incidence has been increasing worldwide. Recognition of the unique clinical and histologic findings of primary breast carcinoma is important to avoid delay in the diagnosis and initiation of appropriate treatment.

In vivo, trastuzumab-vincristine conjugates led to remarkable efficacy when compared to two standards of care, with complete tumor regression just 9 days after single administration. This highlights the untapped potential of the chemotherapeutic arsenal toward the development of novel ADC.

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.

Chemotherapy is more effective in patients with YWBC. We need to pay more attention to this group and achieve individualized treatment, which will facilitate improved treatment of BC and provide new targets and blueprints for clinical therapy.

The absence of calcifications, non-mass lesions, lack of vascularity, and the non-enlarged scope can lead to misdiagnosis of DCIS and DCISM. Understanding the CEUS and clinicopathologic features of DCISM lesions may alert clinicians to the possibility of microinvasion and guide appropriate management.

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.

This study underscores the potential of DL algorithms to predict key genetic alterations, such as TP53 mutations, in BC. DL-based histopathological analysis represents a valuable tool for improving patient management and tailoring treatment approaches based on molecular biomarker status.

Drug sensitivity analysis revealed that the PRG high-risk subgroup was sensitive to inhibitors of BCL-2 family proteins (BCL-2, BCL-XL, and MCL1) and other kinases (PLK1, PLK1, BTK, CHDK1, and EGFR). The PRG risk signature serves as a promising biomarker for evaluating peroxisomal activity, prognosis, and responsiveness to immunotherapy in breast cancer.

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.

The PFS benefit was more pronounced in those individuals who received abemaciclib or ribociclib as second CDK4/6i. Continuation of CDK4/6 inhibition was associated with higher rates of grade 3 and 4 neutropenia (range: 25-40%) and anemia (range: 1.7-11%). In conclusion, switching CDK4/6i and ET conferred a statistically significant improvement of PFS in comparison to ET alone in patients with progression or recurrence on prior CDK4/6i-containing therapy.

We synthesized Fc-PLG-Mal, conjugated DM1 through a "click" reaction, and subsequently bound the resultant compound with the HER2 antibody trastuzumab...HER2-PLG-DM1 significantly inhibited tumor growth in NCI-N87 tumor-bearing mice, achieving a 90.8% tumor inhibition rate, and displayed dose-dependent effects without significant liver and kidney toxicity. These studies offer an efficient and stable method for the preparation of antibody-coupled drugs.

We searched the FAERS database for reports of cardiovascular adverse events in patients with HER2-positive breast cancer receiving trastuzumab, ado-trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd). Proportionate analysis showed age and weight were the two key factors contributing to the occurrence of T-DCs induced MACE. HER2-positive breast cancer patients receiving T-DCs require additional cardiac monitoring, particularly for stroke in younger patients.

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=18, Terminated, BioInvent International AB | Active, not recruiting --> Terminated; After the completion of phase IA, for business reasons it was decided to terminate the study.

P3, N=812, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2032 --> Dec 2030 | Trial primary completion date: Aug 2026 --> Mar 2027

P=N/A, N=25, Active, not recruiting, Centre Oscar Lambret | Recruiting --> Active, not recruiting | Trial completion date: Sep 2023 --> Sep 2025 | Trial primary completion date: Sep 2023 --> Sep 2025

P2, N=25, Recruiting, Guangdong Provincial People's Hospital