Lung cancer is the leading cause of cancer death in the U.S. and throughout the world. Lung cancers are broadly divided histologically into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). About 25% of patients with NSCLC have stage I or II disease. The primary treatment modality is surgical resection,2 and 5-year survival rates are 65% for stage I and 41% for stage II disease. However, more than 70% of patients with NSCLC present with stage III or IV disease. Patients with stage III disease are most commonly treated with chemoradiation, and 5-year survival rate is 26%. Chemotherapy and targeted therapy are often used for stage IV disease, which has a 5-year survival rate of 4%. Tyrosine kinase inhibitor (TKI) is a targeted therapy against specific molecules in critical cell-signaling pathways involved in lung carcinogenesis. The currently available FDA approved TKIs for advanced NSCLC include afatinib, gefitinib, and erlotinib that inhibit epidermal growth factor receptor (EGFR) signaling 6 and crizotinib that inhibits anaplastic lymphoma kinase (ALK) signaling. However, only tumors that carry the corresponding oncogenic mutations (e.g., sensitizing EGFR mutations) would respond well to these TKIs. Meta-analyses of clinical trials evaluating the efficacy of gefitinib and erlotinib have demonstrated that NSCLC patients who are EGFR mutation-positive have a lower risk of disease progression when treated with an EGFR-TKI as compared to those treated with chemotherapy (HR = 0.43, 95% confidence interval, CI=0.38-0.49). EGFR-TKI, however, confers no benefits to patients who are EGFR wildtype (HR = 1.06, 95% CI=0.94-1.19). A phase III trial of crizotinib has also demonstrated the superiority of crizotinib to standard chemotherapy in ALK-positive NSCLC patients (HR = 0.49; 95% CI=0.37-0.64). In Hong Kong, as in other parts of Asia like in China and in Taiwan, other than the majority of lung cancer patients being smokers, there is also a prominence of non-smokers in lung cancer. Compared with Caucasians, there is also a relatively higher incidence of EGFR mutation in lung adenocarcinomas. The prevalence of EGFR mutation in Asian population with lung adenocarcinomas can reach up to 60% compared to at most 30% in the Caucasian population. These EGFR mutant tumors will demonstrate better response to the drug EGFR-TKI, boosting up the response rate to almost 70% compared to 30% with conventional chemotherapy for lung cancer. Even with this remarkable response, however, EGFR-TKI will eventually fail in EGFR mutant lung cancer. There is an imminent need to look for newer therapeutic targets or agents that can overcome this acquired resistance to anti-cancer drugs and to explore alternative molecular signaling pathways that could interact or enhance EGFR signaling pathways to modulate the therapeutic response in lung cancer.
Name: Sequencing of ctDNA in plasma
Description: Types of ctDNA mutationsMeasure: ctDNA mutation Time: an average of one year
Description: Types of new ctDNA mutationsMeasure: Any new ctDNA mutations Time: an average of one year
Description: Quantity of ctDNA mutationsMeasure: ctDNA levels [measured as copy number] Time: an average of one year
Description: Quantity of new type ctDNAMeasure: Any new ctDNA levels [measured as copy number] Time: an average of one year
There is one SNP
Emergence of the EGFR mutation T790M occurs in about 50-70% of patients with acquired resistance to EGFR-TKIs. --- T790M ---