Reversible Premalignant Lesions and Irreversible Cancerous Transformation
According to a report by the Reference News website on April 11, 2021, the April 3 issue of the US magazine Discover posted an article titled "Why Finding a Cure for Cancer Is So Hard," quoting Dr. Todd Golub, director of the Cancer Research Center at the Broad Institute: by the time most cancer patients are diagnosed, they may already have up to ten billion cancer cells in their bodies. This means that an anticancer drug with 99% efficacy still lets one hundred million cancer cells escape—enough to plant the seeds of recurrence.
Moreover, trying to cure cancer is like trying to cure a bacterial infection: while killing bad cells, it also kills many healthy cells, so the treatment itself harms health. Those escaped bad cells, once drug-resistant, easily acquire new mutations as they replicate. The mutated cancer cells that slip through continue to replicate and spread, and the cancer recurs. After recurrence, because the newly mutated cancer cells are more drug-resistant, the previously used drugs no longer work. Generally speaking, once a cancer patient treated by multiple methods relapses, the disease becomes far harder to treat, because the cancer cells in the body have mutated into a new generation with extremely strong drug resistance.
Thus, even today, although we have discovered the mechanism of cancer, curing it remains extraordinarily difficult for doctors worldwide. Japanese cancer patients have relatively long survival times, but it is well known that Japan does excellent early cancer screening; this is the credit of preventive medicine, not a high Japanese cure rate. Cancers caught early are easier to treat.
Some Japanese scholars, such as Makoto Kondo, even argue that the claim of longer survival among Japanese cancer patients does not match the facts: in any country, it takes a long time for early cancer to progress to intermediate or advanced stages. Japanese patients' survival looks long simply because detection is early, adding in the time from early to advanced cancer. Although many scholars consider Kondo's view biased, its reasonable part cannot be ignored. If China's early cancer screening were better, even with no improvement in treatment, our patients' survival figures would look better. So preventing cancer and catching it at an early stage raises residents' average life expectancy; this is beyond doubt.
Cancer is preventable. Prevention first requires vigorously promoting health education, spreading healthy lifestyles, and abandoning bad habits; second, it requires taking premalignant lesions seriously. Many cancers arise from chronic diseases; these chronic conditions that may turn cancerous are called premalignant lesions. For example, gastric cancer premalignant lesions include atrophic gastritis, Helicobacter pylori infection, and gastric ulcer; liver cancer premalignant lesions include hepatitis B, hepatitis C, alcoholic liver disease, and fatty liver; gallbladder cancer premalignant lesions include solitary gallbladder polyps and gallstones.
Generally, the progression from premalignant lesion to cancer is reversible, but once cancerous transformation occurs, reversal becomes very difficult, even irreversible. Many cancers develop from chronic inflammation; effectively treating chronic inflammation helps prevent malignant transformation, but once cancer has set in, conventional anti-inflammatory treatment is useless. Because at the premalignant stage the genes have not yet mutated and do not reproduce without limit. Only after gene mutation does cancer appear; once mutated, genes overexpress, producing large numbers of uncontrolled cancer cells—this is entirely different from the "inflammation" of the premalignant stage.
So why do genes mutate? The answer lies in molecular biology. Under natural conditions, the genes humans inherit are extremely stable: since life began, our inherited genes have replicated 50 billion times yet remain as clear as ever, without major errors. That is why our species has existed for over 5 million years without spawning a new species. Most species on Earth last no more than 10 million years; so if humans cannot escape this natural rule (and indeed it may be hard, because the human Y chromosome is shrinking, meaning our reproductive capacity may one day hit a ceiling—without family planning, our population would naturally decline until extinction), perhaps until the day humankind perishes we still will have produced no new species.
On human chromosome 14 there is a gene called TEP1. The product of TEP1 is a protein component of telomerase, an extraordinary little biochemical machine. The root cause of human aging lies in telomerase; the root cause of the wild growth of cancer cells also lies in telomerase.
As the name suggests, telomerase is an enzyme related to telomeres; precisely, it is an enzyme that repairs telomeres. What, then, is a telomere? A telomere is a short DNA-protein complex at the end of the linear chromosome of eukaryotic cells; short repetitive telomeric sequences, together with telomere-binding proteins, form a special "cap" structure whose function is to maintain chromosomal integrity and control the cell division cycle. Telomeres, centromeres, and replication origins are the three elements that keep chromosomes complete and stable. Telomere length reflects a cell's replication history and replication potential and is called the mitotic clock of cellular lifespan.
We humans age because the number of times our cells can divide is limited; what limits unlimited replication is precisely the telomere. Each time a chromosome replicates, part of the telomere is lost and its length shortens; in certain tissues the shortening is faster. In an 80-year-old, telomere length is only 5/8 of that at birth. Once telomeres shorten to a certain point, the rate of apoptosis far outstrips the rate of new cell production, organs fail, and we die.
Telomerase repairs damaged chromosome ends and re-lengthens telomeres. Telomerase contains RNA used as a template for telomere repair; its protein component resembles reverse transcriptase, the enzyme that enables retroviruses and transposons to proliferate within the genome. Egg and sperm cells can pass genes intact to the next generation because telomerase acts in them. During human embryonic development, the telomerase gene gradually stops being expressed. From that moment on, our telomeres shorten with age until death.
So when telomerase was discovered, many people thought that if we could use it to repair our telomeres, humankind might achieve "immortality." But to this day, for humans, immortality remains an unattainable dream.
For cancer cells, however, immortality is no dream. Because telomerase activity is high in cancer cells, it helps them repair their telomeres, which is why cancer cells can replicate without limit. The most famous example is the HeLa cell, taken from an American uterine-cancer patient and kept alive in laboratories to this day. Most cancer labs worldwide keep HeLa cells, which scientists use as a specimen for studying cancer. Many anticancer pharmacology reports state whether a drug can inhibit HeLa cell growth and reproduction, because those assays were performed on this cell line. Given nutrients, HeLa cells divide without limit, while normal human cells divide only 50–60 times; once a cell in someone's body has divided more than 60 times, it means that cell has turned cancerous and will divide forever.
The key to slowing aging, then, is not letting our cells divide too fast. What speeds up cell division? Human cells divide on average once every 2.4 years; normal cells divide 50 times, which means our theoretical lifespan can reach 120 years, and some long-lived elders exceed even that.
But many of our behaviors and chronic diseases speed up cell division: smoking, drinking, overfatigue, long-term mental stress, chronic inflammation, certain viral influences, and harsh natural environments all damage our cells. Once cells are damaged, new cells must repair the body, accelerating division. Faster division shortens our telomeres and speeds aging. Most cancers are closely tied to aging: only when telomeres become too short is telomerase activated; once activated, some cells gain immortality and become cancer cells.
If we can change some bad habits and halt the damage that certain chronic diseases called "premalignant lesions" inflict on our bodies and cells, the rate of cell division there will slow down and cancerous transformation become less likely. Treating premalignant lesions therefore effectively prevents cancer. As the saying goes, the blessings one can enjoy in a lifetime are limited; if you spend them all too early, life ends too soon. Setting aside genetic influences, people who indulge themselves excessively have faster cell division, die earlier, and face higher cancer risk.