Genetic malformations have long been thought to be the main cause of cancer, but a new study has found that an imbalance in intracellular proteins can trigger cancer. Scientists call this a major breakthrough, revealing a non-genetic mechanism for cancer. The findings, published in Oncogene, illustrate that protein dysregulation is a powerful cancer prediction tool that can determine if a patient is responding to chemotherapy or if a tumor has spread to other sites. The findings open the door to new cancer therapies that target the measurement and prevention of cellular imbalances. Imbalance of two proteins triggers cancer Under normal conditions, cells receive external signals through a cell wall-binding receptor (FGFR2). Upon stimulation, the receptor is turned on within the cell, which initiates the signaling protein and protein kinase pathways that enable cell proliferation. In some cancer cells, this pathway is permanently turned on. The traditional approach to cancer diagnosis is to look for genetically modified receptors that are responsible for keeping the cellular protein pathway on. A scientific team led by the University of Leeds and the University of Texas MD Anderson Cancer Center is focusing on the “AKt signaling pathway” – the protein kinase pathway, an intracellular signaling pathway that drives cancer formation and tumor propagation in vivo. Looking at changes in cancer cells in the absence of external stimuli, it was found that the AKt signaling pathway can be activated in the absence of genetic modifications, and that the relative concentration of Plcy1 and Grb2 proteins competing for binding to the FGFR2 receptor determines which protein ultimately wins the competition. It was found that when Plcy1 levels are high, the AKt signaling pathway is triggered. In this way, an imbalance between the two proteins can lead to cancer cell proliferation and tumor formation. Single gene screening is not enough – non-genetic factors or the key to understanding cancer Human genome sequencing has become a huge investment and there has been the idea that if we know all the genetic information we can predict the risk of cancer and finally treat it with therapies developed based on precision medicine. However, our study shows that single gene screening is not enough. Previous studies have emphasized that the root cause of cancer is genetic mutations. Some studies had pointed out that cancer development is not influenced by genetic factors, for example, not by epigenetic modifications of proteins. However, this study shows that receptors can transmit signals even when they are not activated, so non-genetic factors may be the key to understanding cancer.