English translation of the original Chinese article. Publication dates and the extent of recovered text are preserved. Figures retain their original labels. Read the Chinese original.
Department of Chemistry,University of Waterloo
Keywords: cancer, causes
In the previous instalment, we introduced what cancer is. Today, let us talk about its causes.
Cancer is not a new disease. The earliest case discovered so far comes from human fossils dating to roughly two million years ago. Ancient Egyptian records described cancer as early as 3000 BCE, documenting eight cases and concluding that the disease was “incurable”.
Epidemiological studies in recent years show that the number of new cancer cases is increasing each year. What, exactly, causes this “invisible killer”?
Last time, we discussed how human cells proliferate under precise regulation. How do cancer cells escape this complex regulatory system?
In this instalment, let us examine in more detail how the human body regulates the activities of its various cells. Just as every person in a society is connected to others to a greater or lesser extent, cells in the human body are linked in countless ways. Cells communicate mainly in two ways. The first is through electrical signals, a method used throughout the nervous system. Most communication, however, uses the second method: signalling molecules. Hormones are the signalling molecules most familiar to us. Different cells have a range of different receptors on their surfaces. Particular hormones or other signalling molecules activate these receptors, triggering changes within the cell. This apparently simple approach, rather like “communication mainly by shouting”, has evolved over hundreds of millions of years. Each human cell now has hundreds or thousands of different kinds of surface receptors. Whether each receptor is present, how sensitive it is, and how many copies there are are all precisely regulated. Countless signalling pathways ultimately weave together into a network, forming a communication system more complex than any supercomputer.
Under these conditions, the requirements for the emergence of a cancer cell are very demanding:
1) The cancer cell’s proliferation signals must remain continuously activated.
Signals for cell proliferation are generally produced by other cells. This is rather like a military tally divided between a ruler and a commander so that the commander cannot use the troops to establish independent power. Exceptions do occur, however. One possibility is that a cancer cell secretes its own proliferation-signalling molecules, effectively forging the other half of the tally and activating its own division. Another is that the receptor itself malfunctions, remaining active from the moment it enters service and never needing the other half of the tally.
As mentioned above, the signalling system operates as a network. Generally, activating a proliferation signal also activates another signal that ends proliferation, ensuring that cells stop after growing and dividing for a certain period. In cancer cells, growth-inhibiting signals must be continually ignored, or fail to be produced at all.
2) The cancer cell must be able to proliferate indefinitely.
The vast majority of normal human cells have a countdown to death: each division brings them closer to it. Even under ideal conditions, after 40–60 divisions, cells automatically enter senescence and die. We call this the Hayflick phenomenon. This death is spontaneous. If a cell discovers an irreparable error in its own genes, it may even undergo spontaneous “programmed” death, passing its usable nutrients to surrounding cells in an act of complete altruism. Cancer cells, however, are not bound by this countdown. Studies have found that many cancer cells produce special enzymes after each division to turn the clock back, or simply ignore the death signals altogether.
3) The cancer cell must also evade the immune system.
Even if a cancer cell meets all the requirements above, its surface structure and shape generally show abnormalities to varying degrees. As the final line of defence, a normal immune system can identify abnormal cells and eliminate cancer cells before they gain a foothold. Cancer cells’ ability to slip through is more often due to abnormalities in the immune system itself. This also accords with the higher incidence of cancer among children and older people.
The transformation of normal cells into cancer cells requires “cooperation from within and without”. Internally, changes must occur at the genetic level, whether mutations in the genome itself or abnormalities in the gene-repair system. Externally, there must be insufficient immune capacity, due either to the body or to external factors. The causes of cancer may differ from patient to patient, and new mutations may also occur in a patient as the disease progresses.
As research advances, we are discovering more and more about the causes of cancer. Yet we also marvel at how little we still know about disease, the human body and ourselves. Researchers have a long road ahead. I would like to end with a simple piece of ancient philosophy: “Do not rejoice because of external things, or grieve because of your own circumstances.” A way of life that brings harmony to body and mind will always be of the greatest importance to health. Next time, we will discuss today’s anticancer medicines.
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