Work

Gemcitabine–Ibandronate Conjugate Enables the Bone-Targeted Combination Therapy in Bone Cancer: Synthesis and Efficacy in Combination with Docetaxel

Year: 2021

Type: article

Abstract: Patients with cancer-induced bone disease, including primary bone cancers such as osteosarcoma (OS) and metastases from other tissues of origin, present a high unmet medical need. We present a potential therapeutic approach built upon a proven bone-targeting bisphosphonate conjugate platform with the known synergies of gemcitabine (GEM) and docetaxel (DTX). The synthesis of rationally designed GEM-IB, the conjugate of GEM-5'-phosphate with ibandronate (IB), is presented. GEM-IB as a single agent or in combination with DTX demonstrated reduced tumor burden, preservation of the bone architecture, and improved the survival in a murine model of OS. This is the first demonstration of a bone-targeting conjugate in combination with a second drug to create effective drug ratios in the bone compartment.

Source: Bioconjugate Chemistry

DOI: 10.1021/acs.bioconjchem.1c00507

Authors: Kristen B. Farrell, Shawn Zinnen, Douglas H. Thamm, Alexander Karpeisky

Institutions: MBC Pharma (United States), Colorado State University

Language: English

Topic: Bone health and treatments

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute