ArticleFrontiers in pharmacology2019
Lysosomal P-gp-MDR1 Confers Drug Resistance of Brentuximab Vedotin and Its Cytotoxic Payload Monomethyl Auristatin E in Tumor Cells.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- A Newly Designed Antibody-drug Conjugate Targeting B7-H3 Demonstrates Enhanced Therapeutic Efficacy Across a Spectrum of Cancers.Pharmaceutical research · 2026Article
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Overcoming resistance to antibody-drug conjugates: mechanisms and emerging strategies.The oncologist · 2026Review
- Antibody-drug conjugates in gastric cancer: clinical advances and resistance mechanisms.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Review
- Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.Oncology research · 2026Review
- Beyond approval: a mechanism-based review of novel anti-tumour agents in cervical cancer and when to use them.Frontiers in immunology · 2026Review
- Article
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Exploring Experimental and In Silico Approaches for Antibody-Drug Conjugates in Oncology Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor.Cell reports. Medicine · 2025Article
- Auristatin S: An Auristatin Payload with Improved Tolerability and Modified Bystander Activity.ACS medicinal chemistry letters · 2025Article
- Orthogonal Site-Specific Dual Bioconjugation of Aryl and Alkyl Thiols.Journal of the American Chemical Society · 2025Article
- Antibody-Drug Conjugates Targeting CD30 in T-Cell Lymphomas: Clinical Progression and Mechanism.Cancers · 2025Review
- Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances.Exploration of targeted anti-tumor therapy · 2025Review
- Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration.Biology open · 2024Review
- Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score-matched analysis.Blood advances · 2024Article
- Therapeutic challenges in peripheral T-cell lymphoma.Molecular cancer · 2024Review
- Article
- Antibody-Drug Conjugates in Breast Cancer: Current Status and Future Directions.International journal of molecular sciences · 2023Review
- Payload-Binding Fab Fragments Increase the Therapeutic Index of MMAE Antibody-Drug Conjugates.Molecular cancer therapeutics · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) are composed of an antibody linked to cytotoxic anticancer payloads. ADCs recognize tumor-specific cell surface antigens and are internalized into lysosomes where proteolytic enzymes release the cytotoxic payloads. Efflux transporters on plasma membrane that play a significant role on multi-drug resistance in chemotherapy can be internalized on lysosomal membrane and sequester the cytotoxic payloads. In the present study, ATP binding cassette (ABC) efflux transporters including breast cancer resistance protein (BCRP), P-glycoprotein (P-gp-MDR1), multidrug resistance protein (MRP) 2, MRP3 and MRP4 in lysosomal, and plasma membrane of tumor cells were quantified by targeted quantitative proteomics. The cytotoxicity of brentuximab vedotin and its cytotoxic payload monomethyl auristatin E (MMAE) to the tumor cell lines in the presence and absence of elacridar (P-gp-MDR1 inhibitor) or chloroquine (lysosomotropic agent) were evaluated. MMAE is a substrate for P-gp-MDR1, as the apparent efflux ratio in MDR1 transfected MDCK cell monolayers was 44.5, and elacridar abolished the MMAE efflux. Cell lines that highly express P-gp-MDR1 show higher EC
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