Peto’s Paradox- an innovative approach to cancer treatment
If every cell has a fair chance of becoming cancerous then physically large organism (having large number of cells) and with longer life span should have an increased risk of developing cancer as compared to small, short lived organisms. This kind of correlation between several cells and/or life span of an organism with the development of cancer is not seen in large animals and is called Peto’s paradox. For example, a human lives 50 times longer than a mouse and has 3000 times more cells than mice, yet the rate of cancer in humans and mice is basically the same, whereas blue whales have 3000 times the cells a human has but doesn’t seem to get cancer at all.
. How does cancer develop in an organism?
Throughout the life of a multicellular organism, cells accumulate mutations in several different genes called proto-oncogenes which are caused by endogenous (by cellular mechanisms) and exogenous (environmental carcinogens) processes by which they achieve limitless replicative potential, self-sufficiency of growth signals, insensitivity to anti-growth signals, immunity against immune system. The probability of which should increase with greater number of cells and with longer life spans as more are the chances of tumour initiation, which does not happen.
There are 2 plausible explanations for this paradox. As multicellular organisms grew bigger, they added more and more cells and hence, more of tumour induction. So, they had to develop better cancer defences else they would die (natural selection). The proto-oncogenes (the right mutation in which will cause tumour induction, ability to hide from immune system, call for resources etc.) have an antagonist- tumour suppressor genes (which repair the mutations or signal cell death if it is beyond repair) and it turns out that larger animals have an increased number of them. Because of this elephant cells would require more mutations than mice cells to develop a tumour. Hence, they are more resilient to tumour development than mice. But the solution to the paradox could be something different.
Normally, cells work together in cooperation to form structures like tissues and organs. Cancer cells on the other hand work as independent identities only for their survival by stealing energy and resources from the body which is often the limiting factor for growth of tumours. Tumour cells trick the body to build new blood vessels directly to the tumour itself to feed it. Also, cancer cells are inherently unstable and mutate very quickly, some of them amazingly fast. At some point, a newly mutated cancer cell might suddenly start thinking of it as an individual again and stop cooperating with the original tumour. It forms another tumour fighting for the same scarce nutrients as the original tumour. This newly formed tumour is a Hyper tumour.
This Hyper tumour might cut off the blood supply to the former tumour, starve and kill the original tumour. Cancer killing cancer. This process may keep repeating over and over preventing excessive growth of a tumour. A greater number of Hyper tumours in large animals might be preventing them from having malignant tumours or tumours large enough to cause a problem/be detected. A small 1 g tumour is 5% of the total body weight of a mouse but is only 0.001% of a human and 0.000001% of a blue whale. All the three tumours require the same number of cell divisions and have the same number of cells. An old blue whale might be filled with such small tumours, but it might not care because of insignificant size of the tumour with respect to the whale. Hence, if hyper tumours keep a check on the size and metastatic activity of tumours, they might not cause a problem for an organism.
This is just a hypothesis but could open a very innovative and effective way to treat cancer or better to say- keep tumours in check in humans.