Synchronized Delivery of Proteasome and Bone Marrow Microenvironment Inhibitors in MM

SAN DIEGO — Reversing bone marrow microenvironment (BMM)-induced drug resistance in multiple myeloma (MM) may rely on lipid nanoparticle drug delivery, according to an abstract from the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.¹ Researchers hypothesized that inhibiting the interaction between the bone marrow microenvironment and multiple myeloma cells through the simultaneous delivery of 2 drugs may be a promising approach.

Since the bone marrow microenvironment is thought to drive resistance to proteasome inhibitors and promote tumor growth, and “agents that inhibit the interaction between MM and BMM have been shown to resensitize MM cells to therapy,” the researchers focused on this pathway.

They looked at the nanoparticle drug delivery of bortezomib (BTZ) and ROCK-inhibitor (Y-27632), and discovered this route of delivery inhibited PI3K and MAPK signaling better compared with free bortezomib.

In addition, the synchronized delivery of bortezomib and Y-27632 using PSGL-1-targeted nanomedicine delayed tumor progression and prolonged survival in multiple myeloma significantly better than all other controls in the trial, they noted.

“Altogether, our data demonstrate the ability of PSGL-1-decorated LNPs to specifically target MM-BMM; to efficiently encapsulate and deliver drugs to tumor tissue; to overcome BMM-induced drug resistance in vitro and in vivo, to reduce tumor growth, and prolong overall survival,” the investigators concluded.

Disclosure: The investigators disclosed various ties to pharmaceutical companies in this abstract. For a full list of disclosures, please refer to the original study.

Read more of Cancer Therapy Advisor‘s coverage of the ASH 2018 meeting by visiting the conference page.

Reference

1. Federico C, Muz B, Sun J, et al. Overcoming drug resistance in myeloma by synchronized delivery of therapeutic and bone marrow disrupting agents by nanoparticles targeting tumor-associated endothelium. Poster presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 1931.