In 2000, Dr. Douglas Hanahan and Dr. Robert A. Weinberg, two preeminent cancer researchers, published an article in the journal Cell that outlined the six hallmarks of cancer—the changes that normal cells must acquire to become malignant tumor cells. In all forms of cancer normal body cells go very wrong and begin to grow and proliferate uncontrollably. This transition from a normal cell to a cancerous cell is not simple. To overcome the normal controls and protective mechanisms, cancer cells have to progressively develop several special abilities. In almost all cases, cells that start down this sequence of changes die and are eliminated from the body. However, rarely, cells do complete the gauntlet, acquire all the traits, and produce tumors.
Last year, in March 2011, Drs. Hanahan and Weinberg updated their seminal discussion on hallmarks of cancer with another Cell publication that reviewed recent research on each of the cancer hallmarks noted in the original article and added two additional new hallmarks to bring the total number to eight.
What Are the Hallmarks of Cancer?
Maintaining Proliferative Signals (Hallmark 1): Normal cell growth is carefully regulated through a complex network of hormones and signals within cells. When replacement cells in organs or tissues are required, a chemical growth factor is released that triggers cells to divide and replicate themselves. The first step to becoming a cancer cell is to lock the replication trigger in the "on" position. This is why it is more common to develop cancer in tissues that constantly have to replace cells, such as the intestines, colon, blood, and skin. With a lot of cells replicating, it is easier to get this growth trigger stuck on.
Avoiding Immune Destruction (New Hallmark proposed in 2011 update): When properly doing its job, the immune system recognizes aberrant cells and triggers elimination of them by killer T-cells. However, cancer cells somehow manage to either evade detection by the immune system, or inactivate responding immune cells. It is not well understood how cancer cells accomplish this but a lot of research focuses on trying to subvert this stealthiness and get the body's immune system to recognize and destroy tumor cells.
Evading Growth Suppressors (Hallmark 2): In addition to locking on growth factor triggers for replication mentioned above, there are other signals that prevent cells from dividing even when the growth factor signal say "go." Replicating a whole cell is very complicated and involves a lot of cell components working together. Many things can go wrong so multiple controls are in place to prevent cells from replicating unless conditions are optimal and everything is ready to run the full replication cycle. For example, there are controls in the cell that stop replication if the cell is not big enough, the DNA has too many errors, there is too little of certain chemicals, or not enough oxygen, as well as many other check points. Most of these controls are regulated by tumor suppressor genes, such as the p53 protein or retinoblastoma-associated gene (RB). Typically, at least one of these type of gene is mutated in cancer cells so growth is never suppressed under any conditions.
