Strategies for the targeted delivery of therapeutics for osteosarcoma

Abstract

Background Conventional therapy for osteosarcoma has reached a plateau of 60-70%, a five-year survival rate that has changed little in two decades, highlighting the need for new approaches. Objective I wished to review the alternate means of delivering effective therapy for osteosarcoma that reach beyond the central venous catheter. Methods Drawing on my own experiences providing care to high-risk osteosarcoma patients and reviewing the last two decades of literature describing sarcoma therapy, I summarize available information about potential osteosarcoma treatments that deliver therapy by a less conventional route. Results/Conclusions Intra-arterial chemotherapy has a limited impact on survival, but may help achieve a better limb salvage. Intrapleural chemotherapy is important for managing malignant effusions. Development of inhalation therapies, treatments that target new bone formation such as bisphosphonates, chemically targeted radiation and antibody-based therapies all have potential to improve osteosarcoma therapy.

Overexpression of Smad7 Blocks Primary Tumor Growth and Lung Metastasis Development in Osteosarcoma

“…Approximately 20% of patients have lung metastasis at initial diagnosis and an additional 40% will develop metastasis during the later stages of disease. The presence of metastasis at diagnosis is the most important predictor of disease-free survival with a 5-year survival rate of only 20% for osteosarcoma patients with metastasis compared with 65% for patients with localized disease (5). The standard treatment of osteosarcoma consists of complete surgical resection associated with neoadjuvant and adjuvant chemotherapy composed of 4 agents: doxorubicin, cisplatin, methotrexate or ifosfamide (6).…”

Critical Stages in the Development of the First Targeted, Injectable Molecular-Genetic Medicine for Cancer

“…Indeed, as the development and validation of the world's first (Waehler et al, 2007;Gordon and Hall, 2010), but no longer only (see Reximmune-C; Gordon et al, , 2008, tumortargeted genetic medicine is recognized, the promise and potential of the platform have begun to percolate into the general medical literature, impacting the practice of clinical oncology (Hughes, 2009), medical imaging (Bjojani et al, 2010), medicinal nanotechnology (Peach et al, 2009), and gene therapy (Sverdlov, 2009), as well as the discussions of bedside bioethics (Toh, 2011) and the practical applications of tumor immunology (Zolnik et al, 2010). Looking forward into the future, it is only a matter of time (see Gordon and Hall, 2009) when the progression of metastatic disease is no longer considered to be intractable, and the poor prognosis of chemotherapy-resistant cancer is summarily improved.…”

Identification of candidate drugs for the treatment of metastatic osteosarcoma through a subpathway analysis method

“…However, OS is highly aggressive and numerous patients with OS develop metastases, primarily in the lung, even following resection of the primary tumor (2,7). Furthermore, metastatic OS frequently exhibits resistance to conventional chemotherapies that were effective for treatment of the primary tumor and >30% of metastatic OS cases do not respond to chemotherapy (4,8,9). The chemoresistance of malignant OS limits the effectiveness of current cytotoxic drugs (10).…”