Background: Trastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10-15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR) in the assessment of trastuzumab mediated cardiomyopathy.
Methods And Results: Between 2005-2006 inclusive, 160 breast cancer patients were identified at a single tertiary care oncology centre. Of the total population, 10 patients (mean age 40 +/- 8 years) were identified with trastuzumab induced cardiomyopathy, based on a LVEF less than 40% on serial MUGA or echocardiography. CMR was performed in all patients to determine LV volumes, systolic function and evidence of late gadolinium enhancement (LGE). At the time of diagnosis of trastuzumab induced cardiomyopathy, the mean LVEF was 29 +/- 4%. Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients.
Conclusion: LGE-CMR is a novel way of detecting early changes in the myocardium due to trastuzumab induced cardiotoxicity.
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http://dx.doi.org/10.1186/1532-429X-10-5 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Key Laboratory of Molecular Nanostructure and Nanotechnology, Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria-tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness.
View Article and Find Full Text PDFExpert Opin Drug Saf
January 2025
Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
Objective: The trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan are antibody-drug conjugates (ADCs) that have demonstrated efficacy in the treatment of breast cancer. Nonetheless, these ADCs can also induce severe toxicities in various organ systems, particularly the hematological system. Therefore, this study evaluated the hematological toxicities associated with ADCs in breast cancer based on real-world data.
View Article and Find Full Text PDFIntroduction: Recent advances in the treatment of -mutant non-small cell lung cancer (NSCLC) have led to the development of KRAS inhibitors, such as sotorasib and adagrasib. However, resistance and disease progression remain significant challenges. In this study, we investigated the therapeutic potential of combining trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate, with sotorasib in -mutant NSCLC, while also evaluating HER2 expression in NSCLC samples.
View Article and Find Full Text PDFBioorg Med Chem
January 2025
Department of Pharmaceutical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China; Ningbo Institute of Dalian University of Technology, Ningbo 315016, China. Electronic address:
Betulinic acid (BA) is a kind of naturally occurring lupane pentacyclic triterpenoid, possessing various biological activities including antiviral, anti-inflammatory and antitumor activity. Covalent inhibitors, characterized by electrophilic warheads that form covalent bonds with specific amino acid residues of target proteins, have garnered enormous attention in anticancer agent discovery over the past decade owing to their exceptional selectivity and efficacy. In this study, BA was structurally modified with electrophilic groups, and 23 derivatives of BA were synthesized.
View Article and Find Full Text PDFBreast
December 2024
Department of Clinical Research and Management, Graduate School of Medicine, University of Ryukyus, Japan; Department of Clinical Pharmacology, Faculty of Medicine, University of the Ryukyus, Japan. Electronic address:
Standard trastuzumab therapy can reduce the risk of early recurrence of HER2-positive breast cancer. However, trastuzumab-induced cardiac dysfunction may force the discontinuation of adjuvant trastuzumab therapy. Incidentally, there are still unclear whether or not trastuzumab treatment should be continued in the setting of reduced cardiac function.
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