Investigators at Washington University School of Medicine in St. Louis have developed nanoparticles that carry targeted chemotherapy to tumors that have bone metastases. This strategy, which was developed in mouse studies, lets chemotherapy penetrate the protective environment of bone and minimizes toxic side effects.
In a study published online ahead of print in the journal Cancer Research, the investigators report that docetaxel chemotherapy encapsulated in integrin avb3 targeted nanoparticles may be significantly more effective than standard chemotherapy to decrease bone metastases as well as bone loss and fracture and with significantly less toxicity. They found that docetaxel encapsulated in an integrin avb3 nanoparticle specifically targeted breast cancer bone metastases and was more effective and less toxic than docetaxel alone.
“This approach can be used for all breast cancer patients with bone metastases, since we found that the bone microenvironment induces the expression of avb3 target on breast cancers of all subtypes,” said senior study author Katherine Weilbaecher, MD, professor of medicine at Washington University School of Medicine in St. Louis, Missouri.
Dr. Weilbaecher said integrin avb3 is often expressed on aggressive cancers and has been associated with metastatic spread and resistance to therapy. “We were surprised to find that integrin avb3 was markedly expressed on breast cancer cells that metastasized to bone, but not on breast cancer cells that had spread to lung or liver. We also corroborated these findings in 42 patients of all breast cancer subtypes,” Dr. Weilbaecher told OncoTherapy Network.
She said the latest studies also showed that avb3 was highly expressed on bone metastases compared with the primary breast cancer from the same patient. In addition, the researchers discovered that the bone microenvironment promotes avb3 expression on breast cancer cells.
Dr. Weilbaecher said targeting chemotherapy directly to a cancer cell can decrease side effects and increase delivery of the drug. “Our approach is to improve drug delivery to bone residing breast cancer cells and avoid off target toxicity by using a new type of chemotherapy delivery mechanism,” said Dr. Weilbaecher.
She said bone metastases are the most common site of breast cancer metastasis and the only site of metastatic spread in 40% of patients with metastatic breast cancer. Yet, bone metastases are often resistant to standard chemotherapy. Through a better understanding of the bone microenvironment, there may now be a way to change that.
Co-senior study author Gregory Lanza, MD, PhD, professor of medicine and of biomedical engineering at Washington University School of Medicine, and his team developed avb3-targeted membrane nanoparticles in which the docetaxel prodrug is incorporated into the membrane. “The docetaxel will only be active after the nanoparticle fuses with the avb3 expressing breast cancer cell and delivers the chemotherapy into the cytoplasm resulting in minimal loss of free drug into the blood and little off target side effects,” explained Dr. Weilbaecher.