Serum tumor markers in pediatric osteosarcoma: a summary review

Abstract

Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention.Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine) is an attractive concept for regulation of vascularization in pediatric osteosarcoma.

Autocrine VEGF/VEGFR1 Signaling in a Subpopulation of Cells Associates with Aggressive Osteosarcoma

“…For the purposes of this article, the abbreviation VEGF refers to isoform VEGF-A unless otherwise indicated. Serum VEGF levels are elevated in many patients with cancer, including those with osteosarcoma (6)(7)(8). Inhibition of VEGF effectively suppresses osteosarcoma-induced angiogenesis in a murine model of osteosarcoma (9).…”

Emerging Cytokine Networks in Osteosarcoma

“…A deep understanding of the complex cytokine interplay in oncogenesis may have prognostic significance for the course and progression of osteosarcoma. Special emphasis must be placed on the role of emerging cytokine networks in immunoregulatory and coordinating functions [3] . Bone destruction and pathological bone formation are crucial features in the natural course of osteosarcoma [23] , which implies that several cytokines must be involved in the pathogenesis of these tumours.…”

“…The etiopathophysiology of osteosarcoma is still unknown and the immune response to its development is very individual as well as variable [3] . Gene mutations in the retinoblastoma (RB1) are observed in approximately 50% of osteosarcoma cases and patients with hereditary retinoblastoma are twice as likely to develop the disease.…”

“…It represents approximately 44% of all primary bone tumours among people under the age of 20 [1,3,4] , and is most common among males. Its incidence increases with age throughout childhood, peaking during the growth spurt in adolescence [2,4] .…”

“…It normally develops in areas of rapid bone growth, such as the distal femur and proximal tibia [5] . The most important prognostic factor is the presence of pulmonary metastases that, in most patients, are present in the diagnosis of the disease [3,6] .…”