This may be the best popular science article about cancer!

01Cancer and Tumors

Before we get into the official science popularization, let me first introduce a small question that may bother many people. What is the difference between cancer and tumor?

The words cancer and tumor are often used interchangeably, and generally speaking, there is really no big problem. If you must be confused, there are some differences between the two words. The key word of tumor is "solid", and the attribute of cancer is "malignant", so malignant solid tumors are cancer, blood cancer is not a tumor, and benign tumors are not cancer.

02What causes cancer

What is the most important factor that causes cancer? Genes? Pollution? Diet? Smoking? None of them. The factor most associated with cancer incidence is age!

In 2013, China published the "Annual Report on Cancer" for the first time. It can be clearly seen from the figure below that for both men and women, the incidence of cancer increases exponentially after the age of 40; older men are more likely to get cancer than women, mainly prostate cancer.

Most of the cancers we are familiar with: lung cancer, liver cancer, stomach cancer, rectal cancer, etc. are all old age diseases! Children can get leukemia, but when have you ever heard of a child getting lung cancer or liver cancer? As the average life expectancy of humans increases, it is inevitable that the probability of getting cancer is getting higher and higher. Why do flies rarely get cancer? Because they have a short lifespan and die before they get cancer. Our pet dogs and cats will get cancer because their lifespan can be more than 10 years, which is equivalent to 70 to 100 years old for humans, so the probability of getting cancer is not low.

Are there other factors involved? Of course.

The cause of cancer is gene mutation. There are about 20,000 genes in our body, and there are about 100 genes that are directly related to cancer. If one or more of these cancer genes mutate, the probability of cancer is very high. Why do genes mutate and when do they mutate? Gene mutation occurs when cells divide. Every time a cell divides, a mutation occurs, but most mutations are not on key genes, so the occurrence of cancer is still a low-probability event. When do cells divide? When growing or repairing tissues.

The mathematical formula for the summary is:

The probability of cancer occurring (p) = the number of cell divisions (a) x the number of mutations produced during each division (b) x the probability that the mutated gene is a cancer-causing gene (e)

In this formula, e is the same for everyone, the key is the two factors a and b. I think many causes related to cancer can be derived and explained by this formula:

(a) As we age, our cells need to divide more often, so older people are more likely to get cancer than younger people.

(b) The more damage a human organ suffers, the more repair it needs. Tissue repair requires cell division, so the more times a cell divides. Therefore, long-term organ damage and repeated tissue repair can easily induce cancer. Sun exposure damages skin cells, so the number of sunburns is directly related to skin cancer; smoking or severe air pollution damages lung cells, so long-term smoking can easily lead to lung cancer; eating irritating and contaminated food damages the epidermal cells of the digestive tract, so long-term consumption of spicy and contaminated food can increase the incidence of esophageal cancer, gastric cancer, colorectal cancer, and rectal cancer; chronic hepatitis B virus damages liver cells, so hepatitis B virus carriers are prone to liver cancer, etc.

(c) The number of mutations produced by each cell division is different for each person. This is mainly affected by genetics. Some people are born with some gene mutations. Although these mutations cannot directly cause cancer, they will greatly increase the number of mutations produced by their cells each time they divide. Last year, the famous Hollywood movie star Angelina Jolie wrote an article in the New York Times, saying that she would prevent breast cancer by removing both breasts. The news shocked the world. The reason she made this decision was that her family and she herself carried the BRAC1 gene mutation. With this mutation, the mutations produced by her cell division were 100 times higher than normal. Therefore, many women in her family, including her mother, had breast cancer at an early age. She was estimated to have an 87% chance of breast cancer and a 50% chance of ovarian cancer. From a scientific perspective, her move was a bit impulsive at the time, because there was no guarantee that other parts (especially the ovaries) would not become cancerous, but I still admired her courage. Later, when I heard that Jolie wanted to remove her ovaries as well, I could only think of one word: "a heroic act of cutting off one's arm."

You may want to find out the factors that interest you and see if this formula really applies.

03How is cancer fatal?

The main reason why people are afraid of cancer is because of its high mortality rate. But when it comes to how cancer causes death, many people may not be able to explain it. Why do some people with large tumors get well after surgery, but some people die before their tumors are even seen?

First of all, the severity of cancer has no correlation with the size of the tumor. In 2012, there was a famous Vietnamese named Nguyen Duy Hai who had a tumor at the age of 4. By the time he was 30, the tumor on his right leg had reached an astonishing 180 pounds! During these 26 years, he gradually lost his ability to move, but strangely, he did not have many other symptoms. After the operation, he looked relatively normal. This tumor looks scary, but if it is not located in a critical internal organ, it is actually relatively less harmful to life. This huge tumor is almost certainly a benign tumor, because if it is malignant, it has no chance of growing so large.

What is the difference between benign tumors and malignant tumors?

It is to see whether the tumor has metastasized. Benign tumors do not metastasize and are considered "nail households", so as long as the tumor itself is surgically removed, it is basically cured. Regardless of the size of a malignant tumor, it has already metastasized, and it may be in the blood system, it may be in the lymphatic system, or it may have already spread to other organs in the body. Many cancers (such as breast cancer) generally metastasize to the lymph nodes first, and then along the lymphatic system to other systems, so lymph node puncture examinations are often performed on cancer patients clinically. If there are no tumor cells in the lymph nodes, the patient is at low risk, and the disease can usually be controlled after chemotherapy and radiotherapy.

So how exactly is cancer deadly?

First of all, I have to say that there is no definite answer to this question. Each patient's individual situation is different, and the ultimate cause of death is also different. But generally speaking, it is often related to organ failure, either the failure of a certain organ or systemic failure. Tumors, whether malignant or not, metastatic or not, may compress key organs if they grow excessively. For example, brain tumors often compress important nerves and cause death. Lung cancer grows and fills the space in the lungs, causing the lungs' oxygen exchange capacity to be greatly reduced, and eventually leading to functional failure and death. Leukemia causes the depletion of normal blood cells, resulting in systemic hypoxia and malnutrition, and so on.

If cancer metastasizes, the risk will increase greatly. One reason is that if a tumor metastasizes, it will become many tumors, which will naturally cause great harm. Another reason is that the places where the tumor metastasizes are often very important. The more fatal places are brain metastasis, lung metastasis, bone metastasis and liver metastasis. These three places also have a common feature: due to the importance of the organs, surgery is often very conservative and it is difficult to completely remove the tumor. Therefore, if breast cancer is discovered early, it is generally fine. The breast can be removed surgically, and the patient can live normally for decades. However, if breast cancer metastasizes to the lungs or brain, it is difficult to treat because you cannot remove the lungs or brain completely. Therefore, everyone and their parents must go to the hospital for regular physical examinations every year. If it is discovered a few months earlier, they may live decades longer.

Death from cancer is sometimes not caused by the failure of a certain organ, but rather a system failure. There are many cancers that, for reasons that are not yet clear, will cause patients to lose weight rapidly, and lose muscle and fat rapidly. This is called "cachexia." This process is currently incurable and irreversible, no matter how much the patient eats or how much protein is transfused. Because muscle and fat are essential for the energy supply and endocrine regulation of the entire body, patients will soon experience system failure. For example, the national idol Steve Jobs, who relied on money to support himself, lived for 8 years after being diagnosed with pancreatic cancer. This is no small miracle, but if you look closely at the photos of him before and after the disease, you can clearly see that his muscles and fat have almost disappeared. In the end, he died of respiratory failure.

04Why is cancer so difficult to treat?

When I was growing up, cancer and AIDS were the most terrifying diseases. If you ask me, which will be conquered first, cancer or AIDS, my answer is definitely AIDS.

Why is cancer so difficult to treat? I think there are three main reasons.

The first reason is that cancer is an "endogenous disease". Cancer cells are part of the patient's body. For "exogenous diseases", such as bacterial infections, we have antibiotics. Why are antibiotics so useful? Because they are only toxic to bacteria, but not to human cells. Therefore, antibiotics can be used at very high concentrations, killing all bacteria while the patient is completely cured.

It is not so easy to deal with cancer. Although cancer cells are human cells that have gone bad, they are still human cells. So to deal with them, it is almost a matter of killing one thousand enemies and injuring eight hundred of oneself. This is the "side effect" that everyone often hears. For example, traditional chemotherapy drugs can kill fast-growing cells, which is of course very useful for cancer cells, but unfortunately, there are many normal cells in our body that are also growing rapidly, such as hair follicle cells under the scalp. Hair follicle cells are essential for hair growth. While chemotherapy drugs kill cancer cells, they also kill hair follicle cells. This is why chemotherapy patients lose all their hair. Hematopoietic stem cells responsible for hematopoiesis and maintaining the immune system will also be killed, so the immune system of chemotherapy patients will be very weak and extremely susceptible to infection. The epithelial cells of the digestive tract will also be killed, so the patient will have severe diarrhea, loss of appetite, and so on.

Such serious side effects force doctors to constantly balance between curing cancer and maintaining the patient's basic life, or even "compromise". Therefore, the concentration of chemotherapy drugs must be strictly controlled, and they cannot be used all the time, but must be taken one course at a time.

The second reason why cancer is difficult to deal with is that cancer is not a single disease, but a combination of thousands or tens of thousands of diseases. There are no two leaves in the world that are exactly the same, and there are no two cancers in the world that are exactly the same.

For example, lung cancer is the new top killer among cancers in China. There are nearly 600,000 lung cancer patients in China each year, and 160,000 in the United States. People often ask me: Are there any new drugs for lung cancer in the United States? I say: Yes, but they are only effective for a small number of patients. For example, Novartis' latest anti-lung cancer drug Ceritinib was just approved by the FDA last week. It has a good effect on about 1% of lung cancer. But why is it that the new drug we have been researching for so long is only effective for 1% of patients?

Lung cancer is simply classified according to pathology into small cell lung cancer and non-small cell lung cancer. Are there only these two types of lung cancer? No. We know that cancer is caused by gene mutations, and the number of mutated genes in each cancer is more than one, and they vary greatly. A recent systematic gene sequencing study showed that the average number of mutations per lung cancer patient is close to 5,000! So many variables are randomly combined, resulting in each patient being a little different. The more than 600,000 lung cancer patients in China are actually more like 600,000 different diseases.

Because of the diversity of cancer, pharmaceutical companies are almost destined to develop drugs for only a small number of patients at a time. The cost of developing each new drug? 10 years + 2 billion US dollars! Such a large investment of time and money has led to slow progress. To conquer all cancers, even if it is not a distant future, it is still a long way to go.

The third is the mutation and drug resistance of cancer. This is something that both cancer and AIDS have in common, and it is a headache for everyone. It is also the fundamental reason why we have not yet conquered AIDS.

Biological evolution is a double-edged sword. Nature has given us this ability to adapt to different environments, but cancer cells not only retain the basic evolutionary ability, but also become stronger. In response to the drugs we give them, cancer cells constantly change and try every means to avoid the effects of the drugs. During the clinical trials of Ceritinib, it was found that many cancer cells discarded the mutated ALK gene after a few months of treatment, and generated new mutations to help cancer grow. Such a fast evolutionary speed always makes me sigh at the insignificance of human beings in front of nature.

05 “Early screening” is essential!

When it comes to cancer prevention, "screening" is an indispensable part.

If early detection and early treatment are achieved, the cure rate of some cancers can reach over 90%. Screening for a variety of cancers, including lung cancer, cervical cancer, and colorectal cancer, has been strongly supported by high-level evidence-based medicine. Timely control of some precancerous lesions or early cancers will achieve twice the result with half the effort in cancer prevention and treatment.

06The key to cancer prevention is “anti-aging”

The main cause of cancer is the weakened immune system! A new article in the journal PNAS puts forward a different speculation: with age, the weakened immune system is the more important factor causing the increase in cancer incidence. Moreover, this theory can also explain the phenomenon that men have a higher cancer rate than women.

Cancer Development and a Weak Immune System

However, Professor Thea Newman's team from the University of Dundee, in collaboration with scientists from Heriot-Watt University, the University of Edinburgh and Curie Institute in France, discovered that the bigger reason behind this is not gene mutation, but the declining immune system!

The main reason for the aging of the immune system is the degeneration of the thymus, which is the site of T cell differentiation, development, and maturation and is an important lymphatic organ of the body.

Studies have found that the thymus declines with age, shrinking by nearly half every 16 years on average, so the production of T cells will also decline accordingly. Moreover, the increased incidence of certain cancers is associated with a decrease in the number of new T cells.

The researchers likened the battle between T cells and cancer cells to a "war" in which cancer cells win once a certain threshold is exceeded. They believe that this threshold decreases with age and is proportional to the production of T cells.

As we age, T cell numbers decline, cancer incidence increases

Thea Newman's team analyzed data from 2 million cancer patients aged 18-70 to construct a mathematical equation to assess the relationship between rising cancer incidence and immune system decline, and compared it with the age distribution of 100 different cancers.

The results show that a weakened immune system plays a much greater role in the occurrence and development of cancer than expected, which means that the key to preventing cancer may lie in the immune system rather than genetic mutations.

When facing cancer, no matter whether we are strong or weak, we should not take chances, but take precautions to minimize the risk through healthy diet, proper exercise, regular physical examinations, stem cell anti-aging, etc.