RESUMO
Current standard treatment of patients with high-grade osteosarcoma (HGOS) includes complete surgical resection of the tumor and chemotherapy, most often with high-dose methotrexate, doxorubicin and cisplatin. With this approach > 60% of patients can be cured. However, conventional anticancer drugs have a narrow therapeutic index, and efficacy and toxicity vary considerably among patients. Pharmacogenomics aim to identify key genomic factors for drug effects (either desired or adverse) in normal host cells (germ-line variants) and cancer cells (somatic variants), and if an association between a genotype and a drug phenotype has been identified, validated and demonstrated to have a large effect size, these genotypes may be used to tailor therapy. In addition, pharmacogenomic models can be used to identify novel therapeutic targets. For example, germ-line variants in genes which potentially influence the disposition of methotrexate and cardiotoxicity of doxorubicin have recently been identified. Moreover, next-generation sequencing combined with several analytical methods has identified the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a potential therapeutic target in HGOS. Herein, we discuss whether and how these novel pharmacogenomic insights may help to improve future therapy in HGOS.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Farmacogenética , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Desenho de Fármacos , Genótipo , Humanos , Terapia de Alvo Molecular , Gradação de Tumores , Osteossarcoma/genética , Osteossarcoma/patologia , FenótipoRESUMO
The prognosis after relapse of high-grade osteosarcoma is poor and complete resection of all tumors is essential for survival. A 6-year old was diagnosed with high-grade osteosarcoma and treated according to the COSS-96 protocol. Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and every time it was possible to achieve complete surgical remission. Additional treatments included chemotherapy and dendritic cell-based cancer immune therapy. Since the end of therapy of the 5th relapse, he is alive for 11½ years. Our experience further supports that aggressive surgery can help to achieve long-term survival even in patients with multiple osteosarcoma relapses.