P2, N=25, Active, not recruiting, Mridula George, MD | Recruiting --> Active, not recruiting

P4, N=47, Not yet recruiting, The First Affiliated Hospital of Fujian Medical University; The First Affiliated Hospital of Fujian Medical University

P4, N=161, Not yet recruiting, Xiangya Hospital, Central South University; Xiangya Hospital, Central South University

P4, N=500, Recruiting, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Pierre Fabre (Shanghai) Medical Co.,Ltd.

Against EGFR, curcumin displayed a competitive docking score of - 9.458 kcal/mol and ΔGbind of - 23.00 kcal/mol, closely matching the performance of afatinib (- 10.134 kcal/mol and - 24.28 kcal/mol, respectively)...In the case of AKT1, andrographolide displayed a competitive performance (- 8.044 kcal/mol, ΔGbind: - 32.00 kcal/mol), followed by curcumin and syringolin A. Andrographolide achieved the strongest binding affinity among the natural compounds against HER2 (- 7.006 kcal/mol, ΔGbind: - 21.01 kcal/mol) and ERK2 (- 7.640 kcal/mol, ΔGbind: - 33.00 kcal/mol), outperforming curcumin (- 7.468 kcal/mol, ΔGbind: - 31.23 kcal/mol) and deoxyelephantopin (- 6.517 kcal/mol, ΔGbind: - 29.01 kcal/mol). These results underscore the strong binding affinities of natural compounds to CRC targets and suggest that these compounds, either as standalone agents or in combination therapies, could complement existing chemotherapeutics by overcoming treatment resistance, thereby improving therapeutic outcomes in CRC patients.

P=N/A, N=100, Not yet recruiting, The First Hospital of Jilin University; The First Hospital of Jilin University

P4, N=24, Not yet recruiting, Beijing Chao-Yang Hospital, Capital Medical University; Beijing Chao-Yang Hospital, Capital Medical University

P4, N=200, Not yet recruiting, Henan Provincial People's Hospital; Henan Provincial People's Hospital

No abstract available

No abstract available

P2, N=177, Active, not recruiting, Spanish Breast Cancer Research Group | N=315 --> 177

Many HER2-positive breast cancer (BC) patients relapse within a year of trastuzumab or neratinib treatment. This study identifies new hotspot mutations in HER2 domains II and IV causing trastuzumab resistance. Notably, cells with either wild-type or the examined dimerization domain mutations retained sensitivity to the FDA-approved HER2 kinase inhibitor, tucatinib.

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.

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.

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

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

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.

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

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

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

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.

Our preclinical, structural, and clinical findings indicate 2nd-generation EGFR-TKIs are more effective for EGFRex19ins compared to other TKIs.

Trastuzumab combined with pyrotinib and chemotherapy showed clinical benefits and acceptable tolerance in HER2-positive MBC patients previously treated with trastuzumab. Thus, these combination regimens may be potential options for such patients.

These results show a progressive apparition of genes implicated in EMT, MET, and PDGF pathways in tumors after afatinib. Notably, a list of 13 genes emerged which may contain targets to prevent tumor evolution after anti-HER therapy.

P2/3, N=174, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Dec 2024 --> Jun 2025

P1/2, N=83, Suspended, Virginia Commonwealth University | Trial completion date: May 2026 --> May 2027 | Recruiting --> Suspended | Trial primary completion date: May 2025 --> May 2026

This study could provide potential novel traditional Chinese medicine targets for treating diarrhea caused by tyrosine kinase inhibitor drugs, such as pyrotinib. The study emphasizes the role of TCM in minimizing adverse effects during tumor treatment.

Our findings suggest that the combination of afatinib and bevacizumab may offer long-term clinical benefits for LUAC patients harboring the novel and rare EGFR Q787L mutation. This case highlights a potential therapeutic strategy warranting further investigation in clinical studies.

This case study suggests that the anti-Her-2 regimen involving Disitamab Vedotin and Pyrotinib may offer a potential salvage treatment option for patients with Her-2-amplified mCRC patients. However, further validation in larger cohorts is necessary in future studies.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

This study highlights the high prevalence and detrimental impact of muscle loss during EGFR-TKIs treatment.

P2, N=140, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

Although some instances of adverse events, such as vomiting and reduced white blood cells and neutrophil counts, were evident, these adverse events were grades 1-3. WBRT combined with pyrotinib exhibited exceptional tolerability, showing long iPFS in patients with HER2+ advanced BC and BM.

SPR analysis revealed that cannabinoids bind strongly to HER2-tyrosine kinase (HER2-TK), with CBD showing the highest affinity (K D = 6.16 μM), significantly better than afatinib (K D = 26.30 μM), and CBG demonstrating moderate affinity (K D = 17.07 μM)...In cell viability assays, CBD and CBG effectively inhibited the growth of HER2-positive SKOV3 cells (IC50 = 13.8 μM and 16.6 μM, respectively), comparable to traditional tyrosine kinase inhibitors. These findings underscore the therapeutic potential of cannabinoids, particularly CBD and CBG, as alternative or adjunct therapies for HER2-positive cancers, with the promise of mitigating resistance and adverse effects associated with existing treatments.

T-DXd provides substantial therapeutic benefit for NSCLC patients with HER2 mutations who have had previous treatment but is not deemed cost-effective in either the US or China when compared to docetaxel, nivolumab, and pyrotinib. Price reduction is perhaps the main way to make T-DXd cost-effective.

Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.

P2, N=30, Recruiting, Ruth O'Regan | N=48 --> 30