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Oncolytic Viruses in Lung Cancer Treatment

Introduction to Lung Cancer

Lung cancer, a type of human cancers, is a serious disease that can cause uncontrolled cell growth in lung tissues. As a rule, lung cancer usually starts from the lungs and will spread to many organs and tissues, such as the brain, in the human body. The common symptoms of lung cancer include headache, chest infections, hemoptysis, as well as wheezing. In the past few years of studies, lung cancer has been divided into two main types, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Pilot studies have demonstrated that more than 80% of all lung cancer patients are NSCLC, and SCLC makes up 15% to 20% of all cases.

Meanwhile, many reports have revealed that SCLC grows and spreads faster than NSCLC, making it more susceptible to chemotherapy. Smoking has been considered as the main cause of lung cancers. The data have indicated that people continued exposure to smoke have a high risk of lung cancer. Approximately 90% of patients with lung cancer are smokers. Moreover, several kinds of chemical compounds, such as cadmium, chromium, nickel, are also associated with lung cancer in humans. Up to now, a wide variety of methods have been developed for treating lung cancer, like surgery, chemotherapy, radiation, targeted drugs, and immunotherapy.

Oncolytic Viral Means of Immune Stimulation. Fig.1 Oncolytic Viral Means of Immune Stimulation. (Sivanandam, 2019)

Oncolytic Viruses in Lung Cancer Treatment

In recent years, OVs have been regarded as a powerful tool for the delivery of target genes or potential drugs to various tumors. OVs are capable of replicating in the host and lyse tumor cells to activate and induce strong immune responses against specific tumors. Furthermore, some engineered OVs have been designed by inserting or deleting some genes to improve their performance in oncolytic virotherapy. Many kinds of OVs, such as adenovirus, herpes simplex virus , vaccinia virus, measles virus , and poliovirus, have been genetically modified to kill tumor cells with high safety and efficacy profiles. For example, OVs have been used for delivering candidate drugs to NSCLC. The results have shown that OVs can overcome the issue of intrinsic or acquired drug resistance, which is a promising strategy in pre-clinical studies.

Oncolytic viruses as a tool to eliminate multidrug-resistant lung cancer cells. Fig.2 Oncolytic viruses as a tool to eliminate multidrug-resistant lung cancer cells. (Tseng, 2010)

Besides, there are many stages of clinical trials that have been conducted for identifying the safety and efficacy of OV-based therapy in the treatment of various lung cancer types. Among them, the randomized phase I/ II trial is commonly designed for evaluating the role of oncolytic herpes simplex virus in treating patients with stage IV NSCLC. The data have indicated that no dose-limiting toxicity associated with the drug has been observed in the trial, even at high doses given intravenously. Also, oncolytic viral therapy can induce the complete remission of NSCLC after systemic injection.

References

  1. Sivanandam, V.; et al. Oncolytic Viruses and Immune Checkpoint Inhibition: The Best of Both Worlds. Mol Ther Oncolytics. 2019, 13: 93-106.
  2. Beljanski, V.; et al. The use of oncolytic viruses to overcome lung cancer drug resistance. Curr Opin Virol. 2012, 2(5): 629-35.

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