HER-2 overexpression

Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.

They caused no abnormality in both short- and long-term administrations as well as in healthy mice. In summary, we accomplished significant breakthrough for the therapeutics of intractable lung cancer patients whose cancers become resistant and metastasize.

No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

P2, N=181, Completed, Daiichi Sankyo | Active, not recruiting --> Completed

Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid UC.

Our study demonstrates the tumor enhancing potential of CYLD inactivation in mammary tumorigenesis in vivo and establishes novel relevant mouse models that can be exploited for developing prognostic and therapeutic protocols.

The effect of fusion with the ABD depended strongly on the order of the domains in the constructs, resulting in appreciably better targeting properties of [177Lu]Lu-G3-ABD. Our data suggest that the order of domains is critical for the design of targeting constructs based on scaffold proteins.

HER2 protein overexpression and gene amplification are significantly correlated with shorter OS in Korean women. HER2 can be considered an important predictor of survival outcomes in EC patients.

Moreover, HMAP7 demonstrated remarkable selectivity for HER2, rendering it suitable for use in complex biological systems. Our findings suggest that the novel DNA aptamer HMAP7 holds promise for both therapeutic and diagnostic applications, enabling selective delivery of therapeutic agents or imaging of HER2-positive breast tumors.

P1/2, N=52, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | N=93 --> 52 | Trial primary completion date: Jul 2024 --> Oct 2024

P1, N=11, Terminated, Kyowa Kirin Co., Ltd. | Phase classification: P1/2 --> P1

Unfortunately, although the importance of diagnosis and treatment of high-grade EnCa is well recognized, it is understudied compared to other gynecologic and breast cancers. There remains a tremendous need to couple molecular profiling and biomarker development with promising treatment options to inform new treatment strategies with higher efficacy and safety for all who suffer from high-grade recurrent EnCa.

Under optimal conditions, this ratiometric electrochemical biosensor shows good selectivity and stability with a wide detection range of 1-1 × 106 pM and a detection limit of 78.47 fM. Furthermore, the biosensor exhibits satisfactory anti-interference ability due to the hairpin DNA and dual signal system, and has promising application prospects in the detection of other DNA disease markers.

Moreover, the overexpression of ERBB2/HER2 and TP53 in IBC cases is a topic of ongoing debate, with studies indicating a higher prevalence in IBC compared to non-inflammatory breast cancer. This overview seeks to provide a comprehensive understanding of the histopathological features and diagnostic approaches to IBC, emphasizing the critical areas that require further research.

These results provide insights into the complex interactions between breast cancer cells and the surrounding microenvironment. Further research is necessary to identify the specific factors within breast cancer conditioned medium that mediate these effects and to develop targeted therapies that disrupt this interaction.

P1, N=215, Active, not recruiting, Eli Lilly and Company | Trial completion date: Mar 2024 --> Jul 2024

P2, N=25, Recruiting, University of Southampton | Not yet recruiting --> Recruiting | Trial primary completion date: Nov 2025 --> Mar 2026

P2, N=185, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025

Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target...We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.

P3, N=382, Not yet recruiting, Biocon Biologics UK Ltd | Initiation date: Mar 2024 --> Sep 2024

After intraventricular administration in rats, we demonstrated that the brain-to-blood efflux of Fab was up to 10 times lower than for trastuzumab, associated with a two-fold higher brain penetration compared to trastuzumab. This Fab, capable of significantly reducing brain-to-blood efflux and enhancing brain penetration after intra-cerebrospinal fluid injection, could thus be a new and original effective drug in the treatment of HER2 breast cancer brain metastases, which will be demonstrated by a phase I clinical trial dedicated to women in resort situations.

In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer.

P1, N=48, Active, not recruiting, Carisma Therapeutics Inc | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2023 --> Dec 2024

This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

P=N/A, N=200, Recruiting, Institut Curie | Trial completion date: Nov 2024 --> May 2026 | Trial primary completion date: Jul 2024 --> Jan 2026

Western blotting analysis confirmed that the complexes promote apoptosis by upregulating Caspase-3 and Caspase-9 and downregulating BCL-2. Molecular docking studies unfolded the strong binding affinities of the complexes with VEGFR2, an angiogenic signaling receptor, and BCL2, Cyclin D1, and HER2 proteins typically overexpressed on tumor cells.

Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective antitumor response and clinical benefits to PC patients.

Radiolabeling of DARPin G3-HYNIC conjugates with 99mTc provided the advantage of a single-step radiolabeling procedure; however, the studied HYNIC conjugates did not improve imaging contrast compared to the 99mTc-tricarbonyl-labeled DARPin G3. At this stage, [99mTc]Tc-(HE)3-G3 remains the most promising candidate for the clinical imaging of HER2-overexpressing cancers.

The development of effective therapies with improved response rates and long-term effectiveness is crucial for advanced and metastatic UC. ADCs targeting HER2 show promise in this regard and merit further investigation for UC treatment.

Overexpression of VEGF, PDGF-B, and HER2/neu might be possible prognostic biomarkers in GBC. Poor survival of VEGF and HER2/neu positive cases indicates the possibilities of using their blockers as therapeutic agents.

We noted important differences in co-occurring GA in ERBB2-altered (ECDmut+, KDmut+, amp+) versus ERBB2wt UBC, as well as higher mean TMB and higher APOBEC mutational signature in the ERBB2-altered groups. Our results can help refine future clinical trial designs and elucidate possible response and resistance mechanisms for ERBB2-altered UBC.

This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.

Given the low antitumour activity of existing treatment options in this patient population, trastuzumab deruxtecan might have the potential to fill a large unmet need in HER2-overexpressing NSCLC. Our findings support further investigation of trastuzumab deruxtecan in patients with HER2-overexpressing NSCLC.

In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

In HER2-positive breast cancer, the expression of HOXC8 is elevated in a manner dependent on DNA methylation, and this elevated expression is closely linked to the pathology of the patient. Interfering with HOXC8 expression demonstrates the potential to partially inhibit the development and spread of breast cancer, as well as to alleviate resistance to Herceptin.

This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.

While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

At present, standard of care first-line treatment for those with HER2-positive mCRC remains chemotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors or bevacizumab, depending on RAS/BRAF mutational status and tumor sidedness...While the choice of anti-HER2 therapy is empiric given lack of head-to-head comparisons, the combination of trastuzumab plus tucatinib has received FDA accelerated approval for use in this setting and is generally the authors' preference. Trastuzumab plus lapatinib, trastuzumab plus pertuzumab, and trastuzumab deruxtecan (T-DXd) also have evidence of efficacy in this setting...These include the optimal sequence of anti-HER2 therapies with chemotherapy and anti-EGFR therapies, the optimal combination partners for anti-HER2 therapies, and the incorporation of predictive biomarkers to guide use of anti-HER2 therapies. Results of ongoing studies may thus alter the treatment paradigm above in the coming years.

sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.

Fluorescence imaging further validated the internalization of particles into cells. In conclusion, Trz-Pal-pHSNs emerge as a promising platform for personalized medicine in the treatment of HER2-positive breast cancer.