Single-agent combinatorial cancer therapy

Laboratories all over the world conduct research aimed at developing novel strategies to treat cancer. The approaches include innovative chemotherapy and prodrug agents, therapeutic antibodies, immunotherapies, nanoparticle-based approaches, targeted ultrasound, photodynamic therapy, radiation therapy, biological therapies, and combinations thereof. Recently, live vectors for the treatment and delivery of anticancer agents to tumors have gained considerable interest, primarily because of the ability of a number of microorganisms (bacteria and viruses) to naturally colonize and specifically replicate in tumors. Their natural tropism for cancers makes certain microorganisms ideal for delivery of either conventional or novel therapeutic modalities, but potentially spares patients the adverse effects associated with toxicity to healthy cells. Secondarily, the infection of tumors with microorganisms can elicit strong antitumor immune activation, resulting also in the specific destruction of the malignant cells. At the end of the 19th century, Busch and Fehleisen in Germany and Coley in the United States established the scientific basis for biological therapies by purposefully administering infectious bacteria to cancer patients (1⇓–3). Later, in the middle of the 20th century, interest in tumor-colonizing microorganisms resumed when genetic engineering established the methods by which the genomes of bacteria and viruses could be specifically modified, providing direct control over virulence, attenuation, and the expression of heterologous genes, permitting, for example, the optical imaging of infecting microorganisms (4, 5).