A novel combination therapy that includes sustained-release biodegradable nanoparticles loaded with the cancer drug docetaxel (TXT) is highly effective in halting further progression of cancer bone metastasis in a preclinical model, according to a study published in the journal Biomaterials. These findings offer a promising new approach for treating bone metastasis.
“Advanced stage cancers frequently metastasize to the bone, especially in prostate and breast cancers. Intravenous cancer drugs, however, have difficulty reaching these sites,” said Vinod Labhasetwar, PhD, Staff, Department of Biomedical Engineering, and senior author on the study. “If drugs are not getting where we need them to go in effective doses, we cannot expect them to perform optimally. We clearly need a new way to affect cancer progression once it reaches the bone, and we think nanoparticles may be part of the answer.”
Microscopic substances engineered to deliver large doses of drugs to specific sites in the body, nanoparticles help to deliver targeted treatment and minimize systemic exposure. Dr. Labhasetwar’s team previously showed that biodegradable nanoparticles could effectively deliver paclitaxel (another cancer drug) to the bone and successfully slowed bone metastasis. Here, they decided to investigate TXT, as it is more potent and frequently prescribed for patients with prostate cancer.
In this study, the investigators treated a preclinical model of prostate cancer with either TXT-nanoparticles alone or in combination with the monoclonal antibody denosumab. A pro-cancer protein referred to as RANKL is overexpressed in the bone. Denosumab binds to and blocks the protein’s dangerous effects on bone loss and cancer progression.
Compared to TXT-nanoparticles alone, the combination therapy better stopped growth of the tumors in the bone, prevented bone loss and extended lifespan.
“What is really exciting is that we did not observe any tumor relapse after the therapy ceased, and the bone maintained normal morphology,” noted Dr. Labhasetwar. “Our ability to disrupt the cross-talk between cancer and bone cells that drives cancer progression and bone loss was central to this effect.”
As the research team looks ahead, they are excited to move this investigation into a patient population. The nanoparticles are biodegradable, and both the materials that the nanoparticles are made with and TXT are already approved by the Food and Drug Administration. As such, it should not be long before Dr. Labhasetwar and his colleagues, including researchers from the Cleveland Clinic Genitourinary Malignancies Research Center, can move toward clinical translation.
“The findings from this study are poised to translate to significant, and likely speedy, benefit to patients living with advanced stage cancers that have metastasized to the bone—who unfortunately have to cope not just with the cancer, but also with bone pain, weakness and numbness,” added Dr. Labhasetwar. “New treatments have the potential to improve both a patient’s prognosis and overall quality of life, and we are excited to move closer to fully realizing these benefits for patients and their families.”
The study was funded by the National Cancer Institute (of the National Institutes of Health). Other authors include Sivakumar Vijayaraghavalu, PhD (first author); Yue Gao, MD; Mohammed Tanjimur Rahman, PhD; Richard Rozic, MS; Nima Sharifi, MD; and Ronald Midura, PhD.
Photo credit: Russell Lee