Despite progress in understanding many aspects of malignancy, resistance to therapy is still a frequent occurrence. Recognised causes of this resistance include 1) intra-tumour heterogeneity resulting in selection of resistant clones, 2) redundancy and adaptability of gene signalling networks, and 3) a dynamic and protective microenvironment. I will discuss how these aspects influence each other, and then focus on the tumour microenvironment.
The tumour microenvironment comprises a heterogeneous, dynamic and highly interactive system of cancer and stromal cells. One of the key physiological and micro-environmental differences between tumour and normal tissues is the presence of hypoxia, which not only alters cell metabolism but also affects DNA damage repair and induces genomic instability. Moreover, emerging evidence is uncovering the potential role of multiple stroma cell types in protecting the tumour primary niche.
I will discuss our work on in silico cancer models, which is using genomic data from large clinical cohorts of individuals to provide new insights into the role of the tumour microenvironment in cancer progression and response to treatment. I will then discuss how this information can help to improve patient stratification and develop novel therapeutic strategies.