A new mouse model of osteosarcoma, the most common and fatal type of malignant bone cancer has been developed by researchers at Dana-Farber Cancer Institute, Children's Hospital in Boston.
The 5-year survival rate in osteosarcoma is only about 60pct, and this statistic drops steeply once the cancer spreads. Caused due to dysregulated growth of osteoblasts (the cells that form the bone matrix), osteosarcoma primarily develops near the ends of the femur, tibia or humerus, and is usually diagnosed during adolescence, when the long bones of the body are undergoing rapid growth.
Though, the main causes of osteosarcoma are unknown, it is believed to be caused by two tumor suppressor genes - p53 and Rb, as children with familial mutation syndromes affecting either of these genes have higher incidences of osteosarcoma.
Dr. Stuart Orkin (HHMI, Dana-Farber Cancer Institute, Children's Hospital Boston) and colleagues have developed a novel experimental system to model the genetics of human osteosarcoma. For this they generated a strain of transgenic mice lacking specifically the p53 and Rb genes in an early osteoblast progenitor cell population.
The researchers found that all mutant animals rapidly developed osteosarcomas, with clinical, histo-cytological and molecular features closely recapitulating the human disease.
This led them to conclude that p53 loss is essential for the development of osteosarcoma, and that while Rb gene mutation acts synergistically with p53 loss to facilitate carcinogenesis, loss of Rb, alone, is not sufficient to induce osteosarcomagenesis.
And now, this high-fidelity animal model will further expound the genetic contributions to osteosarcoma, and enable the scientists to rationally design and test new therapies.
"Our work will stimulate translational efforts to develop novel therapies for this devastating bone tumor," said Orkin
The study is published in the latest issue of G and D.