Gene therapy in cancer treatment, clinical applications

Lung cancer is the most common cause of cancer-related deaths worldwide. Despite advances in diagnostics and therapeutics of lung cancer, a 5-year survival rate is still reaching only about 15% [1]. This disease largely affects the socioeconomic statuses of patients and their families, as well as the society. Clinical and molecular evidence has proven that lung cancer is a heterogeneous disease, which demonstrates significant implications in diagnosis [2] and treatment [3]. An increasing number of clinical trials have emphasized targeted and personalized treatments that specifically benefit patients diagnosed by using observed gene expression profiles. The term lung cancer usually refers to tumors that originate from the lining cells of the respiratory tract (epithelial cells) [4]. Based on differences in biological characteristics, lung cancer is classified into two types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts approximately 85% of lung cancer cases [5]. Platinum-based chemotherapy is prescribed as the standard first-line therapy in patients with advanced NSCLC. However, resistance to platinum-based drugs reduces the survival rate which, as a result, has not improved to anything like the extent seen in other cancers [6]. Advances in the understanding of molecular genetics in NSCLC have led to the identification of key genetic aberrations in NSCLC. These genetic aberrations occur in oncogenes that encode signalling proteins that are crucial for cellular proliferation and survival [7]. Genetic profiling has identified driver mutations in over 60% of lung adenocarcinomas, with 9–14% being new targetable oncogenes such as HER2, BRAF, PIK3CA, and RET [8]. SCLC accounts 10–15% of all lung cancer cases and represents the most aggressive subset of lung cancer. Treatment of SCLC has changed minimally over the last few decades. Patients continue to receive non-targeted, chemotherapy regimens consisting of etoposide plus platinum agents, often combined with irradiation. Although SCLC patients respond well to this first-line treatment, relapse is virtually inevitable and resultant tumours are resistant to further therapy [9]. Based on above mentioned information, in lung carcinoma management, the personalized medicine is at the forefront, with the goal to cure patients with a predicted modality to be efficacious based on the molecular characteristics of the tumor. Such approach can offer increase of survival rates of oncopatients, significant reduction of tumor chemoresistence and decrease of a number of potential relapses. Gene therapy can be a powerful weapon to combat lung cancer and to elevate the therapeutic successes.

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