ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2022
Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.Journal of experimental & clinical cancer research : CR · 2026Article
- The real-world safety profile and potential mechanism of isatuximab: Integration of pharmacovigilance and transcriptomic analysis.Medicine · 2025Article
- Targeting bone in cancer therapy: Advances and challenges of bisphosphonate-based drug delivery systems.ADMET & DMPK · 2025Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Engineering small-molecule and protein drugs for targeting bone tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma.Haematologica · 2024Article
- Recent Advances in Minimally Invasive Management of Osteolytic Periacetabular Skeletal Metastases.Seminars in interventional radiology · 2024Review
- A bifunctional bortezomib-loaded porous nano-hydroxyapatite/alginate scaffold for simultaneous tumor inhibition and bone regeneration.Journal of nanobiotechnology · 2023Article
- Morroniside ameliorates inflammatory skeletal muscle atrophyFrontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Limited treatment options exist for cancer within the bone, as demonstrated by the inevitable, pernicious course of metastatic and blood cancers. The difficulty of eliminating bone-residing cancer, especially drug-resistant cancer, necessitates novel, alternative treatments to manipulate tumor cells and their microenvironment, with minimal off-target effects. To this end, bone-targeted conjugate (BP-Btz) was generated by linking bortezomib (Btz, an anticancer, bone-stimulatory drug) to a bisphosphonate (BP, a targeting ligand) through a cleavable linker that enables spatiotemporally controlled delivery of Btz to bone under acidic conditions for treating multiple myeloma (MM). Three conjugates with different linkers were developed and screened for best efficacy in mouse model of MM. Results demonstrated that the lead candidate BP-Btz with optimal linker could overcome Btz resistance, reduced tumor burden, bone destruction, or tumor metastasis more effectively than BP or free Btz without thrombocytopenia and neurotoxicity in mice bearing myeloma. Furthermore, pharmacokinetic and pharmacodynamic studies showed that BP-Btz bound to bone matrix, released Btz in acidic conditions, and had a higher local concentration and longer half-life than Btz in bone. Our findings suggest the potential of bone-targeted Btz conjugate as an efficacious Btz-resistant MM treatment mechanism. © 2021 American Society for Bone and Mineral Research (ASBMR).
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