Gallbladder carcinoma (GBC) is a rare and highly aggressive tumor. Early diagnosis is challenging, which results in a poor prognosis using systemic therapy. Recent studies have identified a subset of GBC patients with HER2 gene (ERBB2) amplification that could benefit from HER2-targeted therapy. Here, we report one patient with recurrent metachronous GBC with metastasis, who received the combination of trastuzumab and lapatinib. This approach achieved a partial response for both the brain and the lung metastases. This study demonstrated that HER2 inhibition is a promising therapeutic strategy for GBC with HER2 amplification and, combined with lapatinib, it can effectively target brain metastasis.
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http://dx.doi.org/10.1177/0300060519847796 | DOI Listing |
Cancer Chemother Pharmacol
December 2024
Departments of Pharmacology, Medicine Faculty, Sivas Cumhuriyet University, Sivas, Türkiye.
Purpose: Human epidermal growth factor-2 (HER-2) targeted drugs are used in only HER-2 overexpressed cancers. However, only a small portion of these cancer types are HER-2 overexpressed. In this study, we aimed to upregulate HER-2 receptors in MCF-7 breast cancer and HT-29 colon cancer cell cultures, which these cells are not HER-2 upregulated in natural status.
View Article and Find Full Text PDFAnn Oncol
December 2024
Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC, USA; Division of Hematology-Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:
Background: In HER2+ early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across 4 neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO and NSABP B-41.
Patients And Methods: We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.
Results: Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-Enriched at baseline (50.
Int J Mol Sci
November 2024
Computational Genomics Division, National Institute of Genomic Medicine, Mexico City 14610, Mexico.
HER2-positive (HER2+) breast cancer is characterized by the overexpression of the ERBB2 (HER2) gene, which promotes aggressive tumor growth and poor prognosis. Targeting the ERBB2 pathway with single-agent therapies has shown limited efficacy due to resistance mechanisms and the complexity of gene interactions within the tumor microenvironment. This study aims to explore potential drug synergies by analyzing gene-drug interactions and combination therapies that target the ERBB2 pathway in HER2+ breast tumors.
View Article and Find Full Text PDFFront Oncol
November 2024
Department of Oncology, Centro Hospitalar Conde de São Januário, Macao, Macao SAR, China.
Fam-trastuzumab deruxtecan (T-DXd) has demonstrated substantial antitumor activity and durable responses in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer. We report here the treatment outcomes of T-DXd in a patient with HER2+ breast cancer with brain metastases that repeatedly recurred and progressed after two lines of salvage therapy. In 2016, a 23-year-old G0P0 female with risk factors including menarche at age 9 years, Li-Fraumeni syndrome, and a strong family history of cancer was diagnosed with bilateral, triple-positive breast cancer.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. Electronic address:
Understanding the capability of a drug to penetrate the blood-brain barrier (BBB) is an unmet medical need in patients with positive human epidermal growth factor receptor 2 (HER2 positive) and brain metastases. The National Comprehensive Cancer Network (NCCN) guidelines recommend the use of tyrosine kinase inhibitors (TKIs) lapatinib, neratinib, and tucatinib in co-administration with monoclonal antibodies or chemotherapy drugs and the antibody-drug conjugates (ADCs) trastuzumab-deruxtecan and trastuzumab-emtansine. Predicting the BBB permeability of these therapeutic agents is a pharmacological challenge due to the various factors involved in the barrier functions.
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