RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer
العنوان: | RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer |
---|---|
المؤلفون: | Laura van 't Veer, Laura J. Esserman, Øystein Garred, Olav Engebraaten, Maria E B Berstad, Christina Yau, Elin Borgen, Anette Weyergang, Ane Sofie Viset Fremstedal, Angela DeMichele, Kristian Berg |
المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications Nature communications, vol 12, iss 1 |
بيانات النشر: | Nature Portfolio, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Oncology, Cell, General Physics and Astronomy, Ado-Trastuzumab Emtansine, Tumour biomarkers, chemistry.chemical_compound, Trastuzumab, Monoclonal, skin and connective tissue diseases, Humanized, Cancer, media_common, screening and diagnosis, Tumor, Multidisciplinary, biology, Detection, medicine.anatomical_structure, Paclitaxel, Female, Pertuzumab, Antibody, medicine.drug, Drug, medicine.medical_specialty, media_common.quotation_subject, Science, Clinical Trials and Supportive Activities, Breast Neoplasms, Predictive markers, Antibodies, Monoclonal, Humanized, Antibodies, Article, General Biochemistry, Genetics and Molecular Biology, Breast cancer, Clinical Research, Internal medicine, Breast Cancer, Biomarkers, Tumor, medicine, Humans, neoplasms, rab5 GTP-Binding Proteins, business.industry, General Chemistry, medicine.disease, 4.1 Discovery and preclinical testing of markers and technologies, body regions, chemistry, Trastuzumab emtansine, biology.protein, business, Biomarkers |
الوصف: | HER2 is a predictive biomarker for HER2-targeted therapeutics. For antibody–drug conjugates (ADCs; e.g., trastuzumab emtansine (T-DM1)), HER2 is utilized as a transport gate for cytotoxic agents into the cell. ADC biomarkers may therefore be more complex, also reflecting the intracellular drug transport. Here we report on a positive correlation between the early endosome marker RAB5A and T-DM1 sensitivity in five HER2-positive cell lines. Correlation between RAB5A expression and T-DM1 sensitivity is confirmed in breast cancer patients treated with trastuzumab emtansine/pertuzumab in the I-SPY2 trial (NCT01042379), but not in the trastuzumab/paclitaxel control arm. The clinical correlation is further verified in patients from the KAMILLA trial (NCT01702571). In conclusion, our results suggest RAB5A as a predictive biomarker for T-DM1 response and outline proteins involved in endocytic trafficking as predictive biomarkers for ADCs. Antibody Drug Conjugates (ADCs) are emerging in the field of precision cancer medicine. Here, the authors suggest using endocytosis as a predictive biomarker for response |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 2041-1723 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::772e45a2f0de058ceab0fc1897c8a893 https://doaj.org/article/e22471ff5b0c4bbbb30060d2218ab799 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....772e45a2f0de058ceab0fc1897c8a893 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20411723 |
---|