HER-2 elevation

Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.

SEVEN revealed unique characteristics of HER2-enriched EVs in cultured cells and complex biological fluid. In combination with current clinical approaches, this method is well poised to support precise therapeutic decisions.

Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.

In summary, our research reveals the molecular mechanisms of irreversible HER2-TKIs in regulating HER2 protein expression by promoting HER2 internalization. These findings advance our comprehension of targeted therapy for GC and provide a promising therapeutic combination strategy with enhanced efficacy against HER2-positive GC.

PIK3CA mutations were significantly enriched, and ERBB2/4 gene mutations were predominant in patients with innate trastuzumab resistance. CTC-DNA sequencing provides new insights into gene alterations associated with trastuzumab resistance in HER2 mGC.

Notably, GSDMB is found to be elevated in Her2-positive gastric cancer cells, providing a rationale for IBI315's efficacy. IBI315 is supported here as a promising bispecific antibody-based immunotherapy approach for Her2-positive gastric cancer in preclinical studies, broadening the therapeutic landscape of this patient population.

Collectively, our computational data suggest that Scutellarein derivatives may serve as potential therapeutic agents for TNBC. However, further experimental investigations are needed to validate these findings.

Staining of tumor sections showed similar HER2 and PSMA expression across groups. In conclusion, these results give no support for any benefit from co-treatment with anti-HER2 antibody for PSMA-targeted radioligand therapy.

Our work demonstrates that β-catenin is highly expressed in BC and it synergically promotes formation and progress of BC with HER2. β-catenin binds with HER2 leading to enhanced interaction with SRC and resistance to trastuzumab.

HR-positive MBC patients with HER2-low and HER2-zero expression responded similarly to endocrine therapy. But HER2-low-positivity in HR-positive MBC may reduce chemotherapeutic effectiveness and HER2 heterogeneity should be taken into consideration.

Enhertu (T-DXd), a HER2-specific antibody-drug conjugate was recently approved as an important therapy for this patient population...Currently, tucatinib is the only HER2-selective small molecule inhibitor approved for metastatic breast cancer in combination with trastuzumab and capecitabine...Additionally, ELVN-002 could provide a meaningful therapeutic option for patients with CNS metastases. ELVN-002 has been selected for clinical development.

GLP toxicity studies using cynomolgus monkeys showed that YL202 is well tolerated with calculated therapeutic index (TI, HNSTD/MED) of ~100 for repeat dosing. No lung or platelet toxicity findings were observed at doses up to the maximum tolerated dose (MTD).Based on these preclinical results, it demonstrates that YL202’s advanced ADC design results in an increased therapeutic margin, and YL201 could be further developed in HER3 positive cancer patients.

After breast surgery, they received 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2). Regardless of HER2 status, doxorubicin altered mitochondrial metabolism prior to the deterioration of cardiac function, indicating the potential of blood metabolomes as non-invasive markers to early detect doxorubicin-induced cardiotoxicity.

Besides, enrichment analyses revealed that protein kinase B signaling was highly correlated to TRKB in Her-2 positive BC. Therefore, TRKB may act as a potential prognostic target and biomarker for Her-2 positive BC.

Elevated HER2 ECD levels were associated with worse PFS (HR 1.74, 95% CI 1.40-2.17; p < 0.001), and this effect was observed in patients treated with chemotherapy (HR 1.81, 95% CI 1.37-2.39; p < 0.001), endocrine therapy (HR 1.91, 95% CI 1.57-2.32; p < 0.001), and trastuzumab (HR 1.74, 95% CI 1.31-2.30; p < 0.001). An elevated sHER2 ECD was an unfavorable prognostic factor in breast cancer but did not affect the efficacy of tyrosine kinase inhibitors such as lapatinib. Detection of sHER2 ECD may be helpful for clinicians selecting the appropriate anti-HER2 therapy for patients with HER2-positive breast cancer.

Methods HER2-CAR-NK cells were developed based on a single-chain variable fragment (scFv) of the widely used humanized monoclonal antibody trastuzumab. Informed consent has been approved by the ECs. The Israeli template of informed consent is in used and it includes study specific information (e.g. study goal, design, method, duration, risks, etc.).

Patient subtypes derived by tissue-based spatial metabolomics are a valuable addition to existing GC molecular classification systems. Metabolic differences between the subtypes and their associations with molecular features could provide a valuable tool to aid in selecting specific treatment approaches.

The result showed that the elevated serum HER2/neu was correlated with the IHC expression of HER2/neu in tissue and the histological grade of the tumor.  Findings suggest that post initial tissue diagnosis (IHC HER2/neu), serum HER2 assay may supplement subsequent tissue tests to monitor disease status and response to therapy.

Based on this data, we posit that selective Rac activation in HER2 positive breast cancers contribute to enhanced cancer malignancy in Puerto Rican patients. This will be validated by a larger sample size of breast cancer tissue comparing HER2/ER/PR status and cancer grade from Puerto Rican (Hispanic) and Caucasian patients.

These have an inverse relationship with Ki67 index elevated values; luminal B HER2-positive subtype has a direct association with HER2 presence; HER2-enriched subtype was statistically significant associated to HER2 presence and elevated Ki67 index values but had an inverse relationship to hormone receptors (ER, PR); triple-negative subtype was strongly associated to Ki67 index values and inversely correlated to ER and PR. We found luminal A subtype as being the most common and luminal B HER2-positive subtype as having the fewer cases.

In conclusion, circ-ERBB2 facilitated Warburg effect and malignancy of TNBC cells by the miR-136-5p/PDK4 pathway, at least in part. This study supported circ-ERBB2 as a prognostic indicator for TNBC.

We believe that overexpression of EGFR/HER2 and PRLR in breast tumors could maximize the actions of their ligands, and further induce cell proliferation promoting malignancy. This could also explain the resistance to endocrine therapy resulting in tumor growth.

Gastric cancer with HER2 positive and elevated serum AFP is a disease with special clinical characteristics . Patients with advanced diseases can be treated with chemotherapy, trastuzumab +/- immune checkpoint inhibitors . This combination is expected to become a new regimen to improve survival of such special patients.

In this review, we will undergo deep molecular profiling of GRP94 in tumor development and summarize the individual roles of GRP94 in common cancers, including breast cancer, colon cancer, lung cancer, liver cancer, multiple myeloma, and others. Finally, we will briefly review the therapeutic potential of selectively targeting GRP94 for the treatment of cancers.

UCHL1 induces DOX-resistance by up-regulating FFA synthesis in HER2+ BC cells. Thus, UCHL1 might be a potential clinical target for overcoming DOX resistance in patients with HER2+ BC.

The HER2 IHC positive rate showed age variation in biopsy specimens of GC. In male the variation was more dramatic than in female. The variation of HER2 positive rate can be attributed to the age variation of the Lauren subtypes.

Whereas loss of PRLR expression in HER2-E breast cancer cells resulted in loss of their luminal differentiation yet enriched for epithelial ALDH+ BCSC population showing elevated HER2-driven tumorigenic, multi-organ metastatic spread, and resistance to anti-HER2 therapy. Collectively, this study defines PRLR as a driver of precise luminal and epithelial differentiation limiting cellular plasticity, stemness, and tumorigenesis and emphasizing the function of pro/forward-differentiation pathways as a foundation for the discovery of anti-cancer therapeutic targets.

Finally, we demonstrate that, in HER2-positive breast tumors, inhibition of EphB4 combined with Lapatinib is more effective than either alone. These findings provide new insights into the signaling networks dictating therapeutic response to Lapatinib as well as a rationale for co-targeting EphB4 in HER2-positive breast cancer.

To our knowledge, this is the largest study to date that has examined the concurrent use of both IHC and ISH HER-2 assays prospectively in a real-time clinical setting. In the IHC 2+ cohort, only 12.5% were amplified by ISH testing. Interestingly, of those in the IHC 2+ cohort not amplified by CISH, 10.8% had an equivocal or excess HER-2 copy number.

These findings provided informative mechanistic insight into the potential application of PHF8 inhibitors to overcome resistance to anti-HER2 therapies.

Our study confirms that 3 T breast H-MRS can be a valid additional tool to obtain further information about breast cancer biology and to predict tumor aggressiveness, because the detection of elevated levels of total choline in the spectrum is associated with a biologically aggressive breast cancer phenotype (large dimensions, grade 3, high values of Ki-67). Our results need to be validated in standardized larger-scale studies.

Human epidermal growth factor receptor-2 (HER-2) overexpression in breast tumor tissues is associated with a poor prognosis but may benefit from treatment with trastuzumab...Thus, serum HER-2 ECD could be a biomarker to identify the subgroup of poorer outcome among HER-2 overexpression breast cancer patients. Inhibition of ADAM10 activity may have potential therapeutic benefit for this most aggressive tumor subgroup.