Optimizing drug delivery for enhancing therapeutic efficacy of recombinant human endostatin in cancer treatment.

Recombinant human endostatin (rhEndostatin) is uniquely able to target neovascular endothelial cells (ECs) and has the potential for antiangiogenetic and antitumor activities. In this review, we explore experimental approaches and clinical trials focusing on drug delivery of endostatin. Continued endostatin therapy can maintain tumors in a state of dormancy, and no signs of drug-induced resistance have been observed. Prolonged delivery of endostatin may be achieved by using pumps (mini-osmotic pumps) or cell encapsulation systems. The largest benefit from rhEndostatin is expected when drug delivery of rhEndostatin is begun as early as possible. Although endostatin has shown promise in controlling tumor neovasculature, a major problem in pharmacotherapy is the side effects of constant drug administration and the limited half-life of antiangiogenic proteins. Gene therapy offers the advantages of maximizing cost effectiveness and maintaining sustained levels of antiangiogenic factors, which may enhance antitumor efficacy. Therefore, we have investigated recent advances in gene delivery of endostatin for cancer treatment. In recent years, preclinical and clinical data have demonstrated the synergistic effects of rhEndostatin combined with other therapies on inhibiting growth of malignant tumors, with minimal toxicity. rhEndostatin has not been proven to prolong the survival rate of patients challenged with cancer when used as single therapy. Thus, we suggest that the combination of rhEndostatin with chemotherapy, radiotherapy, and biotherapy (i.e., fusion protein, molecular-targeted therapy on cancers, etc.) might provide an optimal strategy for cancer treatment.