Patient case: 70-year-old male with non-small cell lung cancer; genetic feature: KRAS (G12C)

Clinical trial: Molecular Epidemiology of Lung Adenocarcinoma in Multi-ethnic Asian Phenotype

Summary: Lung Cancer continues to be the major cause of cancer-related mortality in Singapore. Non-small cell lung cancer (NSCLC) accounts for 75% of lung cancers and adenocarcinoma is the most common histological subtype. Although cigarette-smoking is the main cause of lung cancer, more than a third afflicted in Singapore are never-smokers and 69% affect females. For the majority who present with advanced NSCLC, chemotherapy is the mainstay of treatment. Despite advances made with newer chemotherapeutic agents, it is apparent that the benefit of conventional chemotherapy has plateaued. Efforts toward developing novel treatments based on growing understanding of molecular oncology have yielded drugs that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). They have expanded treatment options for patients with advanced NSCLC. However, monoclonal antibody to VEGF is contraindicated in patients with squamous cell carcinoma due to increased incidence of fatal hemoptysis. EGFR tyrosine kinase inhibitors (EGFR-TKI) appear promising but only 40% of east-asian female never-smokers with lung adenocarcinoma harbour EGFR gene mutations. Estrogen, KRAS, BRAF, ERBE and other genetic mutations can confound response. Molecular data obtained from Caucasian and predominantly east-asian population may not apply to our multi-ethnic groups and our aim is to determine the molecular characteristics of our multi-ethnic asian phenotypes to better understand the process of carcinogenesis and treatment response as well as identify potential novel targets for future drug development. Paraffin-embedded tissues are recalled, and DNA is extracted for mutational analysis, which will be correlated to patient demographics, treatment and outcome.

Detailed description: Lung cancer is a malignant disease of heterogeneous histology and is divided into 2 major groups; small cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC accounts for 75% of lung cancers, and can exhibit different pathways of resistance during treatment. It is increasingly apparent that effective treatment of NSCLC will require multiple drugs that attack different targets. This realization sets the stage for future individualized therapies that will depend on the molecular characteristics of NSCLC to target various pathways.
  AIMS
  1. Describe the molecular epidemiology of lung adenocarcinoma in multi-ethnic asian phenotype.
  2. Correlate tumor molecular characteristics with patient demographics and outcome to better understand carcinogenesis as well as in the discovery of novel targets for future drug development.

Eligibility: Inclusion Criteria:
  -  Asian ethnicity
  -  Age > 21 years old
  -  Non-smoker
  -  Metastatic pleural effusion due to lung adenocarcinoma
  -  Good ECOG status (ECOG 1-2) fit to undergo pleuroscopy and biopsy and agreeable for palliative chemotherapy and or EGFR-TKI
  Exclusion Criteria:
  -  Non-Asian ethnicity
  -  Age < 21 years old
  -  Smoker
  -  Subjects with poor ECOG status or unwilling to undergo pleuroscopy and biopsy
  -  Subjects not suitable to receive palliative chemotherapy or EGFR-TKI
  -  All other histological subtypes and stages of disease

Relevance to patient case: not relevant