Gastric cancer intratumoral heterogeneity: Implications for metastasis and treatment

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related death, with a five year overall survival of 33%. Although it is regarded as a single disease, increasing evidence shows significant clinical, pathological and genomic heterogeneity in gastric cancer (TCGA study). Additionally, not only does gastric cancer differ between patients, but also within the same tumour, so called “intratumoral heterogeneity”. This occurs spatially (in different locations within the tumour) as well as temporally (changes as the disease progresses). Intratumoral heterogeneity has been associated with poorer prognosis in many tumour types, including gastric cancer. The mechanisms behind this are not well elucidated, and implications of heterogeneity on treatment are unknown. The aims of this project will be to: - Better understand extent of gastric cancer intratumoral heterogeneity. - Investigate the impact of heterogeneity on rates of lymph node metastases, and relationship between mutants within primary gastric cancer and lymph node metastases. - Investigate the effects heterogeneity on tumour regression with systemic therapy, and the effects of systemic therapy on heterogeneity of residual tumour.