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Will Oncolytic Virotherapy Be the Winner Fighting Against Breast Cancer?

In 2013, the famous actress Angelina Jolie published her experience of removing her breasts for carrying a genetic mutation which might cause cancer in the future in New York Times, which raised awareness of the public around breast cancer (BC) since then.BC is a malignant tumor that arises within the tissues of the breast. It is the second common cancer in women in the United States, following skin cancer. Each year in the United States, about 245,000 women are diagnosed to suffer from BC, while in men it is about 2,200.The treatment of BC has advanced over the past decade, and besides the common therapies such as surgery, chemotherapy, radiation therapy, hormonal therapy, etc., oncolytic viruses (OVs) have also shown promising therapeutic efficacy.What are oncolytic viruses?Using the virus itself as an active drug transporter, OV is defined as genetically-engineered or naturally virus that selectively recognizes and infects tumor cells, and eventually cause the cells to swell and collapse without harming healthy tissue. Therefore, theoretically, OVs are of higher anti-tumor effects and lower side effects.At present, many kinds of OVs are being evaluated in clinical trials, such as adenovirus, herpes simplex virus, Newcastle disease virus, vaccinia virus and reovirus, which have been proved to be tumor-targeted, non-toxic and capable of inducing powerful anti-tumor immunity.How do oncolytic viruses work to treat breast cancer?Anti-cancer treatment of oncolytic virotherapy works through the following steps(1) OVs directly infect and lyse tumor cells;(2) OVs replicate and infect adjacent cancer cells;(3) The lytic tumor cells release specific antigens and immune-related cytokines, which induce the body to produce strong and durable anti-tumor immune responses;OVs have been proved to be impressive as a standalone treatment agent in preclinical studies of BC. However, the effect is possibly restricted by many factors, such as the tumor microenvironment, host-mounted anti-viral response and pre-existing neutralizing antibodies. Thus, combining OVs with other conventional cancer therapies can improve the therapeutic responses, such as combining with radiotherapy, chemotherapy, and immunotherapy.Current development of oncolytic virotherapy for breast cancerTo date, only one genetically modified herpes simplex virus targeting melanoma was approved by the Food and Drug Administration in 2015. However, in BC research, various viruses have already been extensively tested preclinically to assess their oncolytic efficacy. Currently, there are a number of Phase I and II clinical trials using oncolytic viruses that are completed or ongoing for treating BC patients.While the combination approach remains promising, further challenges still exist. For example, in order to get proper combinations, a wide range of conditions must be considered carefully, such as patient disease progression, prior chemotherapy and resistance, virus receptor expression as well as immune status, which make the treatment highly-customized and complicated.The exploration of oncolytic virotherapy and therapeutic strategies has given new hope to humans to overcome BC. With the further understanding of the biological characteristics of various oncolytic viruses and the deep research of anti-tumor mechanisms, it is believed that OVs will be more effective in clinical treatment of breast cancer in the near future.

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