Context of gene mutations plays important role in non-small cell lung cancer

Lung cancer is a common form of cancer and in many cases, unfortunately, still a poor outcome. Non-small cell lung cancer is the largest subgroup of lung cancer, but targeted therapies are not successful, or after a period of time resistance occurs. Therefore there's a great need to learn more about the underlying mechanisms.

Epigenetics

Researcher Maarten van Lohuizen thinks that possible solutions lie in a better understanding of epigenetics. "In models we try to unravel exactly how genes are regulated. The so-called polycomb repressor complex-2 (PRC2) functions as a large gene switch and turns off large groups of genes. This is crucial for determining the identity of a cell. For example, stem cells must be strictly regulated, if they are going to be too active, this can lead to cancer. "

But in more ways this mechanism plays a role in both the creation and growth of cancer. Van Lohuizen: "What was surprising in our study was that we in models could show that inhibition of PRC2 in lung cancer sometimes worked as a cancer suppressor. However when combined with other cancer-causing mutations, it instead changed cells into a more aggressive variant, characterized by a strong inflammatory response. The problem thus appears more complicated than we thought."

Context

According to Van Lohuizen and his researchers, the context is very important. "Apparently, several mutations are also responsible for determining the outcome of the treatment. This we have demonstrated in models, but also found evidence for in databases with medical records. This is an important first step towards potential new treatment for this very common type of lung cancer."

He thinks in particular of a combination treatment involving PRC2 inhibitors and a simultaneously given inhibitor to the strong inflammatory response, which is already being used in the clinic for other diseases. Whether this combination will indeed work should be reflected in further follow-up research in models, research where Van Lohuizen and his group are currently working on."