Clinical trials investigating mTOR inhibitors like sirolimus and combination therapies with agents such as everolimus and trastuzumab are discussed, underscoring their potential in eradicating BCSCs and improving patient outcomes. In conclusion, targeting the mTOR pathway presents a viable and promising avenue for enhancing breast cancer treatment efficacy by effectively eliminating BCSCs, reducing tumor recurrence, and improving overall patient survival. Continued research and clinical validation of mTOR-targeted therapies are essential to translate these insights into effective clinical interventions, ultimately advancing personalized cancer management and therapeutic outcomes for breast cancer patients.

Metabolomic profiling further highlighted the involvement of the AMPK signaling pathway. These findings provide a basis for future research aimed at developing cancer treatments with reduced side effects.

EGFR-TKIs may be considered as an alternative treatment option for patients with EGFR exon 20 insertions in cases where the currently recommended therapies, such as chemotherapy with or without amivantamab, are either unavailable or intolerable. The potential use of afatinib for specific patients in this context depends on the precise characteristics of their mutation and remains to be determined.

Pyrotinib-based combination therapy is a feasible first-line treatment for HER2-mutant NSCLC, demonstrating significant survival benefits and manageable toxicity. However, brain metastasis patients require enhanced comprehensive management.

The non-m5C carcinogenic roles of NSUN2 may be mediated through interactions with CUL4B, thereby activating the ErbB-STAT3 signalling pathway. NSUN2-mediated upregulation of ErbB-STAT3 pathway enhances the sensitivity of CRC to lapatinib treatment.

This study provides novel insights into CDH3's role in CRC metastasis and its potential as a therapeutic target. The translational potential of CDH3, including its integration with immunotherapy and drug repositioning strategies, offers a promising avenue for the treatment of metastatic CRC.

No abstract available

Hemorrhagic cystitis is a rare complication of combination chemotherapy with docetaxel (TCHP). Clinicians should be vigilant for signs and symptoms of hemorrhagic cystitis in patients receiving docetaxel and alternative treatment option should be considered.

As a proof of concept, we synthesized an HER2-targeting trastuzumab immunoconjugate bearing a NIR-II aza-BODIPY fluorophore...The resulting Trastu-azaNIRII-MMAE selectively accumulated in HER2-positive subcutaneous tumors, significantly reducing the tumor growth. Using NIR-II optical imaging, a single injection of the NIR-II-ADC allowed for the detection of the conjugate over a period of more than one month, highlighting its potential for long-term tracking and therapeutic applications.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P2, N=5, Completed, Amsterdam UMC, location VUmc | Recruiting --> Completed | N=21 --> 5 | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Jan 2024 --> Apr 2024

No abstract available

P2, N=66, Recruiting, Institut Curie | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

P3, N=360, Recruiting, National Cancer Institute (NCI) | Phase classification: P2/3 --> P3 | N=525 --> 360

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2028 --> Mar 2028 | Trial primary completion date: Oct 2025 --> Mar 2026

Moreover, microRNAs-449 overexpression and FASN inhibition decreased cell proliferation and sensitized cells to trastuzumab treatment by inhibiting the PI3K/AKT signaling pathway. Together, these results suggest the microRNAs-449/FASN axis as a potential therapeutic target in combination with anti-HER2 agents to overcome trastuzumab resistance and to improve treatment response in HER2-positive breast cancer patients.

The results reveal a stronger binding affinity between camptothecin and HER2 than EGFR, in contrast to neratinib, which demonstrated affinity exclusively for HER2...Despite its low solubility, the binding stability and pharmacokinetic profile suggest its potential as an effective therapeutic agent for breast cancer, particularly when combined with drug delivery systems that enhance solubility. This work underscores the importance of receptor-specific ligand interactions in drug design and highlights the need for further studies into camptothecin's clinical applications, especially in HER2-positive breast cancer treatment.

To identify adverse event (ADE) signals of three tyrosine kinase inhibitors (TKIs) (Tucatinib, Lapatinib, and Neratinib) used for HER-2 positive breast cancer by utilizing the FAERS database, and to analyze their safety profiles to provide references for clinical risk management. The three TKIs demonstrated distinct ADE signal profiles, with gastrointestinal, systemic, and skin toxicities being the major areas of concern. Future research should validate these findings and develop effective management strategies to enhance treatment safety and improve the quality of life for HER-2 positive breast cancer patients.

This study offers new validation analyses of IRSN-23 in predicting chemotherapy efficacy, showing high reproducibility. The findings indicate the clinical value of using IRSN-23 for refining breast cancer subtype classification, with implications for personalized treatment strategies and improved patient outcomes.

P=N/A, N=308, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Two patients (0.6%) had significant left ventricular ejection fraction decline. Shorter durations of adjuvant trastuzumab have comparable 4-year disease-free survival to standard 1-year therapy and is an alternative adjuvant treatment option for HER2-positive breast cancer patients in resource-limited settings.

A HER2-targeted polymer drug delivery system composed of a 32-arm star polymer (SD) conjugated with the TOP1 inhibitor molecule SN-38, with a trastuzumab antigen binding fragment (HER2-Fab), has been used to target cancer cells overexpressing this receptor...The HER2-SDs demonstrated increased localization with tumor cells rather than in stromal regions, greater penetration into the tumor core and a more homogenous distribution in the tumor section than the untargeted SD. The targeted star polymer conjugated to SN-38 was tested for anti-tumor activity in a HER2-positive gastric cancer xenograft in mice and showed significantly greater efficacy compared to untargeted SDs.

Mechanistic studies unequivocally demonstrate that the primary cytotoxic species is singlet oxygen. These findings suggest that Tz-IR700 could serve as a valuable treatment option for trastuzumab-resistant HER2-positive breast cancer and may also be used as an adjuvant to fluorescence-guided surgery, improving surgical outcomes and reducing the likelihood of tumour recurrence and metastasis.

Patients receiving breast cancer therapy can develop significant GLS change, DD, or CMR-defined CTRCD that can occur in isolation, concurrently, or sequentially. Development of DD is associated with ECV and higher risk for subsequent CTRCD. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

PLGA nanoparticles loaded or decorated with trastuzumab (TZ) were synthesized via a double emulsion protocol and characterized by dynamic light scattering, surface plasmon resonance, transmission electron microscopy, atomic force microscopy, and Fourier transform infrared spectroscopy...In conclusion our studies lay the foundation for future advancements in alternative therapeutic tools for localized breast cancer treatment. The integration of advanced carriers, optical fibers, and microfluidics opens up new possibilities for innovative and targeted therapeutic approaches.

Despite the success of trastuzumab and other HER2-targeted treatments, many patients still experience inadequate responses, highlighting the need for more accurate and accessible biomarkers to predict treatment outcomes...Our study confirms that reductions in sHER2 levels after C2 are a strong indicator of favorable treatment response in HER2-positive BC patients undergoing NAT. Monitoring sHER2 dynamics early in treatment can serve as a useful, non-invasive biomarker to predict pCR and may guide therapeutic decisions in clinical practice.

No abstract available

P1, N=25, Active, not recruiting, Pfizer | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Mar 2025 --> Dec 2025

No abstract available

In the other HER2-positive solid tumor subgroup (n = 34), the ORR was 52.9% (95%CI 35.1%,70.2%). Thus, KN026 plus KN04 exhibits promising efficacy and acceptable safety profiles in HER2-positive nonbreast cancer, as does the 1st-line treatment for GC.

Zanidatamab (ZIIHERA®; zanidatamab- hrii), a bi-specific antibody targeting two non-overlapping epitopes of the human epidermal growth factor receptor 2 (HER2) protein, is being developed by Jazz Pharmaceuticals and BeiGene Ltd under license agreements from Zymeworks Inc., the developer of the molecule, for the treatment of HER2-expressing solid tumours. This article summarizes the milestones in the development of zanidatamab leading to this first accelerated approval for use in adults with previously treated, unresectable or metastatic HER2+ (IHC3+) biliary tract cancer (BTC), as detected by an FDA-approved test.

P3, N=380, Not yet recruiting, EirGenix, Inc.

P2, N=50, Active, not recruiting, Yale University | Trial completion date: Jan 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Mar 2025

The combination therapy reverted the immunosuppressive tumor microenvironment with increased T and NKT cell infiltration. This resulted in successful treatment of advanced orthotopic tumors refractory to CAR-NK cell monotherapy.

We observed TGF-β signaling in HER2-negative tumor regions, which was associated with nonresponder status. These data highlight the biology of intratumoral heterogeneity and the impact of tumor and immune cell features on clinical outcomes and may partly explain the lesser magnitude of pembrolizumab benefit in HER2+ and PD-L1-negative subgroups.

P2, N=42, Completed, Korea University Guro Hospital | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Dec 2024

P1/2, N=34, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P1/2, N=95, Completed, MacroGenics | Phase classification: P1b/2 --> P1/2

Remarkably, after one month of treatment, the tumor showed significant reduction, with mild toxic side effects. Pyrotinib can be used for salvage later-line therapy in HER2-positive advanced EAC with trastuzumab resistance or poor chemotherapy tolerance, which deserves further promotion.

P3, N=354, Active, not recruiting, Takeda | Trial completion date: Jul 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> Sep 2026

P3, N=1524, Not yet recruiting, Alliance for Clinical Trials in Oncology

In December 2024, the HER3 × HER2 bispecific antibody zenocutuzumab was granted FDA Accelerated Approval for the treatment of non-small-cell lung cancers or pancreatic cancers harbouring fusions involving NRG1, the gene encoding the high-affinity HER3 ligand neuregulin 1. In this Review, we provide an essential guide to HER3 signalling and oncogenesis, HER3 expression in cancer and its prognostic implications, oncogenic HER3 somatic mutations as well as rare NRG1 fusions that might depend on HER3 signalling, and the roles of HER3 in resistance to cancer therapies. We also highlight efforts to target HER3 with diverse therapeutic strategies and the potential interplay between HER3 and the antitumour immune response.