Риск развития опухолей после применения рекомбинантных человеческих костных морфогенетических белков

Abstract

Introduction Bone morphogenetic proteins (BMPs) are members of a large family of growth factors known as the transforming growth factor-β (TGF-β) superfamily. BMPs are known for their ability to induce bone formation and successfully used in orthopaedic and neurosurgical applications. Various proteins, such as BMP-2, 4, 7, have been reported to have osteoinductive abilities. Recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human bone morphogenetic protein-7 (rhBMP-7) are widely used for surgical correction of bone defects and spinal fusions. In addition to the effect on bone formation, BMPs also play a role in cell lineage determination, differentiation, proliferation and apoptosis, and BMP receptors are present in many cell types including tumor cells. A large number of studies in vitro and in vivo have examined the role of BMPs as stimulating oncogenesis and metastasis. Therefore, there are some concerns about the use of rhBMPs in clinical practice. Objective In the present study, we aimed to investigate the causal relationship between the use of rhBMPs and oncogenesis by presenting the results of some preclinical and clinical studies. Material and methods For a comprehensive search, we used the following databases: PubMed, Embase, the Cochrane Database and Google Scholar to identifying studies that described a causal relationship between therapeutic use of rhBMPs and oncogenesis. Results The paper represents the findings on the role and identification of molecular mechanisms of BMP involvement in oncogenesis. In addition to that, the studies reporting a risk of oncological diseases with the use of rhBMPs in both preclinical and clinical studies were also analyzed. Conclusion There is a need for further clinical trials in a wide population over a longer timeframe.