Oncolytic virotherapy is an emerging experimental treatment platform for cancer therapy. Oncolytic viruses are replicativecompetent viruses that are engineered to replicate selectively in cancer cells with specified oncogenic phenotypes. Multiple DNA and RNA viruses have been clinically tested in a variety of tumors. This review will provide a brief description of these novel anticancer biologics and will summarize the results of clinical investigation. To date oncolytic virotherapy has shown to be safe, and has generated clinical responses in tumors that are resistant to chemotherapy or radiotherapy. The major challenge for researchers is to maximize the efficacy of these viral therapeutics, and to establish stable systemic delivery mechanisms.

GVAX is a GM-CSF gene-transduced tumor vaccine. Expression of the GM-CSF gene within either autologous or allogeneic tumor cell populations has demonstrated evidence of immune stimulation in patients and evidence of antitumor activity particularly in prostate cancer and non-small-cell lung cancer. Results of preclinical studies justify clinical investigation. A summary of clinical results is presented.

An understanding of onco-cardiology or cardio-oncology is critical for the effective care of cancer patients. Virtually all antineoplastic agents are associated with cardiotoxicity, which can be divided into 5 categories: direct cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction, cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced repolarization abnormalities. Radiation therapy can also lead to coronary artery disease and fibrotic changes to the valves, pericardium, and myocardium. All patients being considered for chemotherapy, especially those who have prior cardiac history, should undergo detailed cardiovascular evaluation to optimize the treatment. Serial assessment of left ventricular systolic function and cardiac biomarkers might also be considered in selected patient populations. Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Antiplatelet or anticoagulation therapy might be considered in patients with a potential hypercoagulable state associated with chemotherapy or cancer. Open dialogue between both cardiologists and oncologists will be required for optimal patient care.

BackgroundMetastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties.MethodsThis phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m2 cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints.ResultsSix objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin.ConclusionAcceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.

The melanoma differentiation-associated gene-7 (MDA-7) was isolated while screening for upregulated genes in terminally differentiated melanoma cell lines. Preclinical studies attempted to test the theory that oncogenesis arises from a cellular differentiation process culminating in dysregulation of the cell cycle and ultimately malignancy. The MDA-7 gene (gene symbol IL-24) has been classified as part of the IL-10 family of cytokines demonstrating significant anticancer potential. Preclinical studies have shown that MDA-7/IL-24 is effective in inducing cancer cell death by several pathways in various tumor models. A Phase I clinical trial studying intratumoral injections of solid tumors showed evidence of clinical activity with limited toxicity. This small trial suggested therapeutic potential. Results are reviewed. Future opportunities involve combination with different gene delivery systems with systemic potential.

Desmoid fibromatoses are benign, slow growing fibroblastic neoplasms, arising from musculoaponeurotic stromal elements. Desmoids are characterized by local invasion, with a high rate of local recurrence and a tendency to destroy adjacent structures and organs. Desmoid fibromatoses are rare in children, and though they may occur in the head and neck region, are extremely rare in the paranasal sinuses. Here we report a case of extraabdominal desmoid fibromatosis in a seven-year-old boy involving the sphenoid sinus, one of only six published reports of desmoid fibromatosis of the paranasal sinuses. The expansile soft tissue mass eroded the walls of the sphenoid sinus as well as the posterior ethmoid air cells extending cephalad through the base of the skull. We discuss the clinicopathologic features of this lesion, including structural and ultrastructural characteristics, and we review the literature regarding treatment and outcome.