The emergence of oncolytic virotherapy not only revolutionizes the standard of cancer treatment but also innovates the concept of cancer treatment. the advantages and disadvantages of oncolytic virotherapy. was used by Connell to treat advanced cancers, and tumor regression was observed not long after that (11). Later, in the 1950C1970s, live viruses were deliberately injected into cancer patients and showed positive activity, such as Egypt 101 West Nile virus (4/34 transient regressions), adenovirus lysates (26/40 showing localized tumor necrosis), and Urabe strain mumps virus (37/90 complete remission or partial responses) (9). However, some side effects were emerging Z-VEID-FMK in these early researches by using natural viruses, because these viruses were not engineered for tumor selectivity, especially in immunosuppressed patients with leukemia or lymphoma (five of eight patients had severe encephalitis after being treated with West Nile virus) (9, 12). The OV has become a promising treatment to fight cancer in Z-VEID-FMK the new era. It is reasonable to believe that oncolytic virotherapy has the potential to become one of the primary therapies to treat cancer. The emergence of oncolytic virotherapy not only revolutionizes the standard of cancer treatment but also innovates the concept of cancer treatment. It is called the third revolution of tumor treatment after traditional chemotherapy and targeting therapy. The primary purpose of this review is to present the latest advances in clinical applications or trials of various OVs and to look forward to the future based on the current shortcomings of OVs. The Origin and Development of Oncolytic Virus Treatment The concept of using viruses to treat tumors has been around for more than 100 years. As early as 1904, a 42-year-old woman with leukemia was reported to have had her tumor receded due to influenza. Then, in 1912, Italian doctors found that rabies vaccine injection can cause cervical cancer regression, which led to the emerging concept of OV therapy and Rabbit Polyclonal to EPS15 (phospho-Tyr849) a series of related studies (13). In the 1950s and 1970s, the researchers conducted a lot of clinical trials using wild-type viruses for the treatment of tumors, but due to the inability to effectively control the pathogenicity of the virus, the OV settled at the second place in cancer therapies. It was not until the 1980s that the emergence of genetic engineering technology made it possible to modify the genome of a virus, followed by the emergence of genetically engineered attenuated and highly selective viruses. In 1991, preclinical animal experiments reported that the gene-modified human herpes simplex virus I (HSV-1) by knocking out thymidine kinase (TK) could inhibit the growth of glioma in mice, prolong the survival of mice, and have excellent safety. In 1996, onyx-015, a genetically modified adenovirus, entered phase I clinical trials (14, 15). In 2004, RIGVIR, a non-pathogenic enteric cytopathic human orphan virus, was approved in Latvia for the treatment of melanoma and became the first OV approved by regulatory authorities for cancer treatment. In 2005, the modified adenovirus H101 (Oncorine, recombinant human adenovirus five injection, ankeri) was approved Z-VEID-FMK in China, but its clinical efficacy has not been internationally recognized (16). In October 2015, the Food and Drug Administration (FDA) approved the marketing of T-VEC (talimogene laherparepvec, Imlygic). In 2016, T-VEC was approved to market in Europe and Canada, marking the maturity of OV technology for the treatment of cancer. Currently, three OV products have been approved for marketing, and six more OV products are in phase III clinical studies (17). Compared with other tumor immunotherapies, OVs have many advantages, such as high killing efficiency, precise targeting, fewer side effects or drug resistance, and low cost (18). All of these make oncolytic virotherapy a promising therapy to fight cancer compared with surgical therapy, chemoradiotherapy, and targeted therapy. The OV contains a wide range of viruses that have Z-VEID-FMK some common characteristics that virotherapy relies on. Malignant cells are more susceptible to OV infection because of the specific cytokines they expressed. On the one hand, it is reported that tumor-driver mutations enhance the selectivity of viruses in cancer cells (19, 20). Furthermore, many tumor cells supported the replication of selective viruses, maybe because of the lack of antiviral type I interferon signaling (21). In addition to this part, the size and complexity of different OVs are diverse, such as vaccinia [190 kilobases (kb)] and HSV1 (152 kb) to the tiny parvovirus H1 (5-kb linear, single-stranded DNA) (22, 23), which may lead to differences in the ability of the virus to infect tumor cells. The Application of Oncolytic Virus Three viruses currently in medical use, RIGVIR, Oncorine, and T-VEC, have shown satisfactory therapeutic effects. Besides, many OVs are in preclinical tests; among them, herpesvirus, adenovirus, and vaccinia disease presented good experimental results. Below,.