Abstract
Currently, lung cancer treatment has been developing in several approaches such as; conservative chemotherapy or novel targeted therapies which increase the overall response rate, survival rate with good quality of life for the patients. Thus, this research project’s goal is to explore the molecular alterations in Thai lung cancer patients which could be different from the other ethnicities. The result of this research will lead to targeted drug development in Thailand for Thai lung cancer patients. The final result of molecular alterations in 159 Thai lung cancer patients (178 tissue samples) from this research project by NGS method from both FFPE and fresh frozen tumor tissue (initial analyzed only the common mutations in lung cancer) showed EGFR mutation 54.7%, BRAF mutation 10.1%, KRAS mutation 28.3%, and MET exon14 splice site 8.8%. We also found 37 patients (23%) whom had more than one gene mutation. These results were very interesting and different from the other countries’ results, especially BRAF and MET exon14 splice site mutation which occurring only < 4% incidence in other populations. BRAF and MET inhibitors are in the clinical development. Furthermore, we confirmed the tumor heterogeneity of lung cancer from our study in 14 patients. One out of 3 patients had different gene profile in different organ at the same time. The other 2 patients had same gene profile even in different organ. Eight out of 11 patients had the different gene profile when they developed disease progression in different organ. These results are very interesting and very useful for exploration of resistant mechanism in lung cancer and developing targeted therapy drug for lung cancer patients. In addition, our research team also found 3.7% of EML4-ALK translocation and 1.3% of CD74-ROS1 translocation which currently we already have the targeted drugs for these two types of fusion genes. PDL1 expression is one of our interesting predictive and prognostic biomarker. We demonstrated that high PDL1 expression (≥ 1%) significantly correlated to higher stage of lung cancer disease (stage 3 and 4) which also had the worse prognosis compared to the early stage lung cancer. EGFR-positive lung cancer patient with high PDL1 expression (≥ 1%) also had significantly poor responded to EGFR-TKI and shorter survival compared to those with low PDL1 expression (< 1%) [16.3 vs. 25.0 months HR = 3.0 (1.17-7.73), P = 0.023]. These findings are very useful for the further drug resistant research together with targeted and immunotherapy drug development in the future. Even though we explore the diagnostic technique and the approach for lung cancer treatment as mentioned above, but the cancer prevention is also very important for the oncology world right now. The previous literatures reported the role of Metformin (anti-diabetic drug), Aspirin (anti-platelet drug), and Statins (lipid lowering agents) in decreasing cancer incidence rate, but the results were not homogenous and most of studies were small population-based studies only. These 3 groups of drugs involve in the metabolism of human body, thus cancer metabolism is the important and interesting field which could lead to cancer prevention in the future. This research project also focuses in cancer metabolism and cancer prevention by studying the largest and longest follow-up of population-based study in Thailand (EGAT database: Electricity Generating Authority of Thailand). Our final results showed ASA, Statins, and Metformin did not significantly decrease the cancer incidence rate. Alcohol drinking and increased aging significantly increased risk of gastrointestinal cancer. Hepatitis virus B carrier also significantly increased risk of liver cancer. However, this report had several of limitation due to nature of retrospective study, but it is very interesting and fascinating to explore more in term of cancer prevention with these group of drugs in prospective study. In this study, we also explored about serum metabolomics profile in 38 early stage lung cancer patients whom underwent surgery. We will report the final result in 75 patients next year. We found the significant changing in amino acid, biogenic amines, sphingolipids, and glycophospholipids in patients’ serum before and after surgery. It is very interesting that tryptophan was significantly increased while glutamate was significantly decreased after surgery. Kynurenine, a biogenic amine which use tryptophan as the initial compound, was also significantly increased after surgery. These finding are very useful to develop immunotherapy and predictive biomarker for immunotherapy. It is also useful to further explore in cancer prevention. In conclusion, the study of molecular alterations in Thai lung cancer patients is very important for targeted drug development in order to drive the innovative lung cancer treatment. However, the other important issue and concern is cancer prevention. Nowadays cancer is the most leading cause of death in Thailand and cancer also causes a lot of burdens in Thailand and Global public health. We believe that cancer metabolism is one of the key factors for cancer prevention in the future which could probably help to prevent and decrease the cancer incidence rate and solve the cancer burden in Thailand.
