Translational biology of osteosarcoma

Abstract

For the past 30 years, improvements in the survival of patients with osteosarcoma have been mostly incremental. Despite evidence of genomic instability and a high frequency of chromothripsis and kataegis, osteosarcomas carry few recurrent targetable mutations, and trials of targeted agents have been generally disappointing. Bone has a highly specialized immune environment and many immune signalling pathways are important in bone homeostasis. The success of the innate immune stimulant mifamurtide in the adjuvant treatment of non-metastatic osteosarcoma suggests that newer immune-based treatments, such as immune checkpoint inhibitors, may substantially improve disease outcome.

Using a Family History Questionnaire to Identify Adult Patients with Increased Genetic Risk for Sarcoma

“…However, 41% of those with an identifiable TP53 mutation did not meet the classical lfs or Chompret lfl criteria 17 . The fact that our only patient with a TP53 mutation met neither of the foregoing diagnostic criteria illustrates the challenge in detecting TP53 FIGURE 2 Phenotype, genotype, and pedigree of a 48-year-old woman with a germline MSH2 mutation.…”

“…Similarly, although the less-specific and more-sensitive Birch and Eeles definitions of lfl syndromes 12,13 have identified TP53 mutations in families that would have been missed by stricter criteria, a great preponderance of the families fulfilling those criteria have not been shown to harbour identifiable germline mutations 14,16 . Mutations in other genes can also sometimes predispose to osteosarcoma and other types of sarcoma 17,18 .…”

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…Osteosarcomas are bone-forming tumors characterized by the presence of an extracellular osteoid matrix produced by cancer cells and associated with a very complex local environment including bone cells, blood vessels, stromal cells and immune infiltrates [3][4][5][6]. The osteosarcoma cell is the tumorous counterpart of osteoblast.…”

Alternol, a natural compound, exerts an anti‐tumour effect on osteosarcoma by modulating of STAT3 and ROS/MAPK signalling pathways

“…Current therapies include surgical resection and combination neo‐adjuvant chemotherapy (doxorubicin and cisplatin with or without methotrexate) cure less than 70% of patients 2. However, the survival of patients with metastatic or relapsed OS has remained virtually unchanged over the past 30 years, with an overall 5‐year survival rate of approximately 20%.…”