| Summary: | 博士 === 國立中興大學 === 生物醫學研究所 === 103 === Lung cancer is the leading cause of cancer-related death both worldwide and in Taiwan. In a recent decade, epidermal growth factor receptor (EGFR)-targeted therapy has emerged as a novel and effective strategy in lung cancer management. Activating mutations of EGFR gene are the most common genetic alterations in lung cancer in Eastern Asians, and serve as an important predictor of EGFR-tyrosine kinase inhibitors (TKIs) efficacy. Herein, we focused on the association between the detection of EGFR mutations and the efficacy of EGFR-TKIs in lung cancer patients.
The present study contained three major parts. In the first part, we showed that plasma cell-free DNA could be an alternative specimen for EGFR mutation testing. Furthermore, changes in plasma EGFR mutation status can be successfully assessed using the PNA-ZNA PCR clamp method and can serve as an independent outcome predictor. In the second part, we demonstrated that a significant portion of the erlotinib responses in EGFR-wild type lung adenocarcinoma patients were related to the limitations of detection methods. We emphasized that not only direct sequencing but also mutant type-sepcific sensitive methods were unable to detect EGFR mutations in some patients. In the third part, we showed that a significant proportion of lung squamous cell carcinoma (SCC) patients would derive a clinical benefit from erlotinib treatment. The objective response rate of erlotinib in lung SCC patients was much higher than the frequency of EGFR mutations. One of the possible explantations is that erlotinib might target additional pathways other than the EGFR mutations. Further studies are needed to prove this concept.
In the present study, we explored the limitations of current EGFR detection methods, evaluated peripheral blood as an alternative specimen for EGFR mutation testing and looked for patients other than EGFR-mutant population who could potentially benefit from EGFR-TKIs treatment. These results may lead to the application of EGFR-TKIs to more lung cancer patients and drive the era of targeted therapy going a step further.
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