New treatment of bone metastases
In the battle of modern medicine with malignant diseases, effective remedies, as a rule, have undesirable and even dangerous side effects.
Chemotherapy certainly saves lives, but its side effects complicate the lives of patients.
A group of researchers from Princeton University, New Jersey, in collaboration with the pharmaceutical company Amgen, has identified 15D11 antibodies that fight bone metastases. They "turn off" the protection of cancer cells from chemotherapy and increase its effectiveness.
Most often, patients die not from the primary tumor, but from its metastases. The researchers studied the mechanisms and ways of breast cancer metastasis in the body.
Special attention was paid to bone metastases, the interaction of cancer cells with bone tissue cells. Earlier studies demonstrated the important role of Jagged1 molecules, which helped breast cancer cells metastasize into bone tissue. The 15D11 antibodies described in this study are capable of blocking Jagged1 molecules.
In healthy bones, two processes constantly occur: the destruction of old tissue by osteoclasts and the growth of a new one in its place due to osteoblasts.
In cancer patients, these processes may not work correctly. For example, osteoclasts begin to continuously corrode bone tissue until the bone is completely destroyed. Or vice versa, osteoblasts can ensure the growth of the tumor, taking it for normal bone tissue and protecting it from the effects of chemotherapy drugs. In other words, osteoblasts, in fact, can become a cradle protecting tumor cells.
Fluorescent image of metastatic tumor cells (green) after chemotherapy (left) and chemotherapy in combination with 15D11 antibodies (right). Without the action of 15D11, osteoblasts (red) surround cancer cells (green). The nuclei of healthy and cancer cells are colored blue. Source: KangLab/PrincetonUniversity.
Initially, the researchers assumed that 15D11 would work only in those areas where there is a high content of Jagged1 molecules. Contrary to expectations, 15D11 antibodies in combination with standard Jagged1 chemotherapy were more effective than isolated 15D11 treatment, even in those tumors where the Jagged1 content was low.
Chemotherapy is usually weakly effective for bone metastases. At the beginning of treatment, the tumor decreases, but then osteoblasts begin to produce Jagged1 molecules that protect the tumor from the effects of chemotherapy drugs. 15D11 antibodies destroy the "shield" of osteoblasts, thereby reducing the resistance of tumor cells to chemotherapy and increasing the effectiveness of treatment.
In order to prove the leading role of osteoblasts and the Jagged1 molecules they produce in tumor resistance to chemotherapy, a study was conducted on mouse models.
Three-dimensional fluorescent image of osteoblasts (red), which are located around cancer cells (green) and protect them from the action of chemotherapy drugs. The nuclei of healthy and cancer cells are colored blue. 15D11 antibodies prevent osteoblasts from protecting cancer cells and increase the effectiveness of chemotherapy. Source: KangLab/PrincetonUniversity.
In the group of mice treated with combined chemotherapy and antibodies, the greatest effect was observed compared to mice treated in isolation with chemotherapy or 15D11 antibodies. In one experiment, bone cancer was reduced by more than 100 times with combined treatment.
Such an impressive effect, perhaps, was observed for the first time. The technique has been studied for metastases in the bones of breast cancer, but the authors do not exclude that it will be equally effective for localization of the primary tumor in another organ, for example, for metastases in the bones of prostate cancer.
The authors hope that the work on preparing the 15D11 antibody preparation for human testing will take a little time, because this can be a big and important step forward for oncology.
Article by Hanqiu Zheng et al. Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy is published in the journal Cancer Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Princeton University: A new weapon against bone metastasis? Princeton lab develops antibody to fight cancer.