While most scientists have viewed genetic aberrations as the primary cause of almost all cancer, a new study of ovarian cancer at the University of Leeds in the United Kingdom and the University of Texas MD Anderson Cancer Center suggests that cancer may be caused "solely by protein imbalances within cells." Published in the journal Oncogene and reported in Science Daily, the research shows how "protein imbalance is a powerful prognostic tool, indicating whether or not patients are likely to respond to chemotherapy and whether a tumor is likely to spread to other sites." This study could also lead to new therapies designed to measure and prevent dangerous protein imbalances in cells, the article explains (http://www.sciencedaily.com/releases/2015/07/150727092537.htm).
According to the American Cancer Society, cancer, the second most common cause of death in the US, accounts for nearly one of every four deaths. The World Health Organization estimates that, worldwide, there were 4 million new cancer cases and 8.2 million cancer-related deaths in 2012 (http://www.medicalnewstoday.com/info/cancer-oncology/).
According to the lead author, Professor John Ladbury, Dean of the University of Leeds' Faculty of Biological Sciences and Professor of Mechanistic Biology, "There has been huge investment in sequencing the human genome with the idea that if we get all the relevant genetic information we can predict whether you have a predisposition to cancer and, ultimately, use a precision medicine-based approach to develop a therapeutic approach. Our study demonstrates that genetic screening alone is not enough."
The study concentrated on the "Akt pathway," a signaling pathway inside cells that drives cancer formation and the spread of cancers through the body. Normally, the cell would get external signals by means of a cell wall-bound receptor (FGFR2, in this research). Because of this stimulus, the receptor becomes "switched on" inside the cell, thus triggering the recruitment of signaling proteins and the initiation of the Akt pathway, which has the function of getting the cell to proliferate. According to the article, "In some cancerous cells, this pathway is permanently switched on. A conventional approach to diagnosing this cancer would be to look for genetic modification of the receptor (or recruited proteins), which could be responsible for maintaining the switched on state."
The researchers studied isolated cancer cells that did not have external stimulation and determined that the "Akt pathway" could be set in motion without genetic modifications. They found that two proteins -- Plc?1 and Grb2 -- compete for attaching to FGFR2. The relative concentration of these proteins determines which one does the binding. When Plc?1 succeeds, it stimulates the Akt pathway. Thus, an imbalance in the amount of the two proteins can trigger cell replication and cancer formation.
Now the researchers are studying the same mechanisms in other kinds of cancer. In addition, they are looking at other cell receptors that might play a role in sustaining oncogenic signaling without being activated.