Selectively Replicating Oncolytic Adenoviruses Combined with Chemotherapy, Radiotherapy, or Molecular Targeted Therapy for Treatment of Human Cancers

Oncolytic adenovirotherapy presents a novel approach for cancer therapy. Oncolytic adenoviruses are modified to replicate and induce oncolytic cell death in cancer cells but not in normal somatic cells. The first oncolytic adenovirus to be developed was ONYX-015, an E1B-55. kDa gene-deleted oncolytic adenovirus; after which many inventive oncolytic adenoviruses have followed. H101, an oncolytic adenovirus with very similar gene constructs as ONYX-015, was approved in China as the world's first adenovirus cancer treatment in humans in 2005. Many clinical trials have revealed that oncolytic adenoviruses produce synergistic antitumor effects in combination with conventional chemotherapeutic agents, radiation, and some molecular targeted agents, although monotherapy with oncolytic adenoviruses shows limited effects. In this chapter, we discuss the developments of oncolytic adenoviruses, focusing on their synergistic effects when combined with other treatment modalities. Then we discuss the problems that must be overcome for adenoviruses to become more attractive as cancer treatment agents and to expand their clinical applications.