ArticlePNAS nexus2022
SLC46A3 is a lysosomal proton-coupled steroid conjugate and bile acid transporter involved in transport of active catabolites of T-DM1.
Article in PNAS nexus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 25 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026Review
- Navigating Antibody-Drug Conjugate Sequencing in Gastric Cancer: Cross-Resistance Biology, Target Switching, and Decision-Making Frameworks for the Post-Progression Landscape.Current oncology reports · 2026Review
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport.Nature communications · 2026Article
- EGFR- and HER3-targeted bispecific antibody-drug conjugate demonstrates antitumor activity in metastatic castration-resistant prostate cancer.The Journal of clinical investigation · 2026Article
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cuproptosis inducers mediate cold lethality via SLCR-46.1 in C. elegans.Nature communications · 2026Article
- Impact of Oral Pre-Exposure Secretory IgA Prophylactic Produced in Rice on Gut Microbiome Homeostasis.Pharmaceutics · 2026Article
- Antibody-Drug Conjugates in Oncology: Principles, Clinical Development, and Future Directions.MedComm · 2026Review
- Overcoming resistance to antibody-drug conjugates: mechanisms and emerging strategies.The oncologist · 2026Review
- Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A mechanistic pharmacokinetic-pharmacodynamic model for degrader-antibody conjugates.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- VARIDT 4.0: distribution variability of drug transporters.Nucleic acids research · 2026Article
- Antibody-drug conjugates in gastric cancer: from targeted cytotoxicity to immune modulation.Frontiers in immunology · 2026Review
- Precision oncology in gynecologic cancers: molecular taxonomy, biomarker-guided therapeutics, and the challenge of therapeutic resistance.Frontiers in oncology · 2026Review
- A class of benzofuranoindoline-bearing heptacyclic fungal RiPPs with anticancer activities.Nature chemical biology · 2025Article
- Antibody-drug conjugates in breast cancer: current resistance mechanisms and future combination strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- The mechanisms of HER2 targeted ADCs are dependent on Rab GTPases.Therapeutic advances in medical oncology · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics that enable targeted delivery of cytotoxic drugs to cancer cells. Although clinical efficacy has been demonstrated for ADC therapies, resistance to these conjugates may occur. Recently, SLC46A3, a lysosomal membrane protein, was revealed to regulate the efficacy of trastuzumab emtansine (T-DM1), a noncleavable ADC that has been widely used for treating breast cancer. However, the role of SLC46A3 in mediating T-DM1 cytotoxicity remains unclear. In this study, we discovered the function of SLC46A3 as a novel proton-coupled steroid conjugate and bile acid transporter. SLC46A3 preferentially recognized lipophilic steroid conjugates and bile acids as endogenous substrates. In addition, we found that SLC46A3 directly transports Lys-SMCC-DM1, a major catabolite of T-DM1, and potent SLC46A3 inhibitors attenuate the cytotoxic effects of T-DM1, suggesting a role in the escape of Lys-SMCC-DM1 from the lysosome into the cytoplasm. Our findings reveal the molecular mechanism by which T-DM1 kills cancer cells and may contribute to the rational development of ADCs that target SLC46A3.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.