Genetic malformations have long been thought to be the main cause of cancer, but a new study has found that an imbalance of proteins within cells can trigger cancer. Scientists are calling this a major breakthrough that sheds light on the non-genetic mechanisms of cancer. The findings, published in Oncogene, illustrate that protein imbalance is a powerful cancer prediction tool that can determine whether a patient is responding to chemotherapy or whether 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 cell wall binding receptors (FGFR2). Upon stimulation, the receptor is turned on inside the cell, which initiates the signaling protein and protein kinase pathway for cell proliferation. In some cancer cells, this pathway is permanently turned on. The traditional way of diagnosing cancer is to look for genetically modified receptors that are responsible for keeping the cellular protein pathway switched on. The scientific team, led by the University of Leeds and The University of Texas MD Anderson Cancer Center, focused on the “AKt signaling pathway” – the protein kinase pathway, an intracellular signaling pathway that drives cancer formation and tumor spread in vivo. Observing changes in cancer cells in the absence of external stimuli revealed that the “AKt signaling pathway” can be activated in the absence of genetic modification. two proteins, Plcy1 and Grb2, compete for binding to the FGFR2 receptor, and the relative concentration of the proteins determines which protein ultimately wins in 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 far from enough – non-genetic factors or the key to understanding cancer Sequencing the human genome has become a huge investment, and there has been an idea that if we know all the genetic information we can predict cancer risk 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 key to understanding cancer.