Clinical Research Directory

Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

Currently, tyrosine kinase inhibitor (TKI) remains the standard of care for oncogene-driven non-small cell lung cancer (NSCLC). However, almost all oncogene-driven NSCLCs would develop acquired resistance against TKI in clinical practice. Therefore, understanding the molecular mechanisms underlying the acquired resistance is a critical issue in lung cancer. Based on the literature, acquired resistance mechanism against EGFR TKI includes EGFR secondary mutation (T790M, C797X, L792X, G796X, L718Q, and exon 20 insertions), MET amplification, HER2 amplification, acquired gene fusions, and other complex alterations. From the perspective of mutagenesis, the acquired resistance against TKI may be associated with APOBEC mutational processes, kataegis, chromothripsis, extrachromosomal DNA (ecDNA), and the interaction among them. However, still 30% to 50% of oncogene-driven NSCLCs had no identified mechanism attributed to the acquired resistance. Previous studies mostly used targeted-gene sequencing, which may overlook some structural variation and the transcriptomic dynamics. This study aims to investigate the genomic alterations, mutational processes, and the transcriptomic landscape underlying the acquired resistance using integrated genomics.

Feasibility Study of Tissue and Blood Collection in Oncogene-addicted and Neoadjuvantly Treated Non Small Cell Lung Cancer

This study aims to determine if it is feasible to collect samples of blood and viable lung cancer tissue in patients with either: * Stage IV mutation-driven NSCLC * Stage II-III NSCLC undergoing neoadjuvant immunotherapy prior to surgery Viable tissue has been defined by the collaborating pathology department as the presence of viable tumour cells, in accordance with recommendations from the International Association or the Study of Lung Cancer. In patients with stage IV NSCLC, obtaining adequate samples of viable tissue for advanced testing can be challenging, as sites of cancer that are accessible by biopsy are often small, and contain few viable cancer cells. If obtained, however, viable blood and tissue specimens can be utilised for genetic and other analyses aimed at identifying cancer markers that may offer prognostic information, or that may potentially lead to development of therapies that target these markers in the future. In patients with stage II-III NSCLC, the use of immunotherapy prior to surgery has been shown to affect the proportion of viable tumour tissue at the time of surgery, although this needs to be further studied. There is a need to better understand the genetic basis of these tumours to improve response rates to immunotherapy prior to surgery. The study will be open for four years in total. The first three years will consist of recruitment and participant follow up, and the fourth year will consist of follow up only. Data analysis will occur in the fifth year when the study is closed.