Goding Group: for non-scientists
Whereas once it was believed that all cancer cells within a patient were the same, it is now clear that they are very different from each other. Cancer cells exhibit a great deal of differences between the sequences of the DNA that they contain. This so-called genetic diversity accumulates as cancer progresses. In addition, cells within a tumour, a mass of cancer cells, can also adopt fundamentally different states dependent on the nature of their surroundings. Low oxygen or nutrients, or signals coming from the patient’s immune system, can cause even cells with identical DNA sequences to behave differently. The combination of genetic alterations that promote cancer initiation, combined with changes in the environment within tumours cause cancer cells to become invasive and spread within the body. Both genetic and non-genetic variation is responsible for therapy resistance. Our work, primarily using melanoma skin cancer, is aimed at understanding how the environment of cancer cells causes them to adopt an invasive or therapy-resistant state. We focus on non-genetic mechanisms since, unlike genetic mutations, these changes are potentially reversible and are therefore druggable; we have already shown that is it possible to convert drug-resistant cells to drug-sensitive cells. We realised that cancer cell invasion is underpinned by a mechanism related to the response to starvation. Cell migration in response to starvation is designed to ensure survival of the organism and is an adaptation conserved from bacteria through to man. We are therefore exploring whether disrupting this adaptive response would be a good strategy to kill cancer cells exposed to the stresses encountered within tumours.