Cancer: The Whole Shebang
When I was 10, my dad was diagnosed with gallbladder cancer. He went through multiple treatments, all with the hope of getting better. However, he died a year later.
Each year 9.5 million to 10 million people die from cancer worldwide. Around 1.9 million people in the United States were diagnosed with cancer in 2020. Of those 1.9 million, about 606,500 people died. 39.5% of people will be diagnosed with cancer during their lifetime. Roughly 16,900 children and teens in the United States were diagnosed with cancer in 2020, and about 1,750 died from it.
So, clearly, this is an issue.
What is cancer?
Cancer happens when cells grow out of control, which can cause tumors. Cancer cells grow without having signals telling them to grow, and they don’t stop or die when told to.
When a tumor forms it sends out chemical signals that force blood vessels to create new paths towards the tumor. These new blood vessels supply nutrients, oxygen, and they get rid of waste from the tumor. Angiogenesis is the process of creating new blood vessels.
What causes cancer? 🧬
DNA damage is the overall cause. DNA damage can be caused by genetics, where some genes alter the DNA and cell function. The cell will reproduce with the altered DNA, creating more copies and mutations. Another cause of damage is cellular reproduction errors, which happen by chance as cells reproduce. These are typically natural mutations, so it could be luck of the draw to get cancer. 😕 Lastly, there are some causes of damage that you can control. These include but aren’t limited to exposure to UV rays (ex: sunbathing without sunscreen ☀️), smoking 🚬, and eating a lot of processed food 🍟. Over time, these activities can change DNA, which could lead to cancer.
All mutations — no matter the cause — add up. It is estimated that there must be 6 mutations before cancer forms.
The genetic changes that cause cancer mostly affect proto-oncogenes, which are responsible for normal cellular growth and division; tumor suppressor genes that keep check on abnormal growth; and DNA repair genes, which fix DNA when it gets damaged. If DNA repair genes don’t function properly, the DNA will reproduce with the damage, leading to mutations.
What are conditions can become cancer?
Hyperplasia is when cells in the tissue multiply faster than normal. The cells, however, look normal under a microscope.
Dysplasia occurs when cells build up (just like hyperplasia), but they look abnormal. The more abnormal the cells, the more likely there is to be cancer.
Carcinoma in Situ is a group of abnormal cells (a tumor) in tissue. It doesn’t spread through the body, though. It also isn’t technically cancer, yet, but is sometimes called “stage 0.”
Types of Cancer
There are a ton of types of cancer, so this list could go on forever . I’ll spare you, though, and limit it to just a few.
Carcinoma is the most common type of cancer. It is formed with epithelial cells, which are cells that line the surfaces of the body, including inside and outside surfaces. In the category of carcinoma, there are many specific types of it: adenocarcinoma, basal cell carcinoma, squamous cell carcinoma, and transitional carcinoma.
Sarcoma is found in bones and soft tissues. Osteosarcoma is common and in the bones. Some sarcomas that are in tissues include leiomyosarcoma, Kaposi sarcoma, malignant fibrous histiocytoma, liposarcoma, and dermatofibrosarcoma protuberans.
Leukemia is found in the blood-forming tissue of the bone marrow. With leukemia, abnormal white blood cells build up and block normal cells from getting through. This makes it harder for tissues to get oxygen, as red blood cells carry oxygen. It also makes it harder to clot and fight infections.
Lymphoma starts in the lymphocytes, specifically called T-cells or B-cells. T-cells and B-cells are part of the immune system. With lymphoma, abnormal cells build up in the lymph nodes, lymph vessels, and other places. The two main types of lymphoma are Hodgkin lymphoma and Non-Hodgkin lymphoma. Hodgkin lymphoma is from Reed-Sternberg cells, which are large, abnormal cells. Reed-Sternberg cells are developed from B-cells. Non-Hodgkin lymphoma is a larger category. Cancers here can grow fast or slow and be from B-cells of T-cells.
Melanoma starts in cells that turn into melanocytes, which make melanin/skin pigment. Melanoma stays mostly on the skin, but it can be found in colored tissue (like the eye).
There are so many more types of cancer, nevertheless, these are five of the main types.
Cancer Growth
Cancer starts with one abnormal cell or a small group of abnormal cells. The cell keeps growing and pushing out other cells. It then can create a tumor, which will send chemical signals to get blood vessels to the tumor. The blood vessels let the tumor grow more because they provide nutrients and oxygen to the tumor.
Genes make DNA grow and replicate in a controlled way. The DNA is the basis of what tells the cell how to behave, so if the DNA is damaged or changed, it changes the cell’s behavior. Genes get damaged frequently, but cells usually can repair the damage. Over time, though, the damage can build up and get out of control.
Cells fuel their growth largely with amino acids (proteins). Excluding glutamine, amino acids make up 20–40% of the cell’s mass. Also, normal cells use glucose for energy, but tumor cells use fermentation.
How does cancer spread?
First, let’s get some definitions out of the way. Metastatic cancer is cancer that has spread around the body. Metastasis is the process of cancer moving through the body. When cancer is metastatic, it is harder to cure. Last definition: the primary tumor is the initial tumor. However, some cancers don’t form solid tumors!
Cancer starts to spread around stage 4 cancer. When it spreads, cancer looks just like it did when it was in its original location. To clarify, different locations with cancer have cancer cells that look different, but metastatic cancer looks like the cancer cells you would find in the first location.
Cancer cells can spread more quickly because they don’t have molecules that attach to other cells and hold them in place. This makes it easier for them to separate from the other cells.
There are five main steps for cancer to spread. I’ll explain each briefly.
- Grow/invade nearby tissue
Cancer cells go through the membrane into nearby tissue. At this point, a tumor must have already been formed to continue metastasis. - Move into close by lymph nodes or blood vessels
Using angiogenesis, the tumor produces chemical signals to get blood vessels to grow towards it. The tumor benefits from the new blood vessels, and, as cancer progresses, cancer cells can break off and spread through the bloodstream. - Travel through the lymphatic system or bloodstream
Going through the bloodstream puts a lot of tension on the cell, so many will die. However, a few survive. Also, most cells don’t reach this point. - Go through blood vessel walls in a different location and move into new tissue
To go through the blood vessel into a new location/new tissue, the cancer cell will go under even more stress, partly because the tissue it’s invading is healthier (in most cases) than the one it came from. - Grow in new tissue, form a tumor, and support the tumor
This final step is where the cell reproduces uncontrollably again and forms a tumor. To keep the tumor alive, it does angiogenesis, as it did before.
Lastly, there are different kinds of spreading. Transcoelomic spread is where cancerous cells get through surfaces covering body cavities and get into body cavities(ex: liver). Hematogenous spread is metastasis that invades blood cells and spreads through the bloodstream. Lymphatic spread invades lymph nodes. It can go through the entire body via the lymphatic system.
Cancer and Reproducing
Cells communicate with chemical signals. Cancer either interprets the signal incorrectly or receives the signal as a different signal than it should have been. This causes cancer cells to behave differently, which is why cancer cells can grow in a petri dish 🧫. (Yes, you read that right). Normal cells cannot do this. However, cancer cells can because they don’t need growth signals to grow (they behave differently). They basically make their own growth signals that happen to always be on.
For multiple reasons, including the one above, cancer cells can reproduce much faster than regular cells. Normal cells only divide 40–60 times before they can’t divide anymore and die, whereas cancer cells can divide many more times. Part of why cancer cells can divide more is because they have the ability to repair the wear-and-tear on the ends of chromosomes. An enzyme in cancer cells called telomerase reverses this wearing down.
So, why can cancer reproduce so quickly? Well, there are multiple reasons for this. One is that cancer cells don’t “mature,” meaning they don’t have specific tasks. FYI, the maturing process is called differentiation. Okay, back to what I was saying: This creates a sort of spiral effect. The cells reproduce quickly, which makes them not have time to mature. Now, they won’t function properly, making them be able to grow faster. Since they’re dividing quickly, the new cells will have a greater chance of inheriting mutations and mistakes. The new cells will be even less mature than the previous one, which lets them divide faster. (See where it’s going?) This process continues.
Now we’re going to get into the more detailed and specific details. To speed up development and reproduction, positive regulators will be overactive, and negative regulators — tumor suppressors — will be less active.
Oncogenes are overactive forms of positive regulators. Remember when I said proto-oncogenes are affected by the genetic changes that cause cancer? That means they can become cancerous oncogenes.
Mutations that turn proto-oncogenes into oncogenes can include amino acid changes. The arrangement of the amino acids can be changed, thereby altering the protein it creates. This can make the protein always be “on.”
Other mutations can include amplification, where a cell gets an extra gene and starts making too many proteins. The increase of protein can cause the cancer cell to reproduce faster. Also, DNA repair errors can cause the switch from proto-oncogenes to oncogene. When DNA is being fixed, it can accidentally connect proto-oncogenes to other genes, which makes a new protein. This new protein isn’t regulated, and can therefore get out of control.
Tumor suppressors can be non-active or non-functional when there is cancer. If they aren’t functioning properly, they can’t stop the tumors. The protein p53 is the most commonly mutated.
P53 is crucial to the cell’s response to DNA damage; when DNA is damaged, a sensor protein will turn on p53, which will stop the cell cycle by using a cell cycle inhibitor. The cell cycle is stopped at the G_1 checkpoint, which is where cells decide if they should continue to divide or not. While the cell cycle is stopped, DNA repair enzymes will try to fix the DNA. If they succeed, the cell can reproduce/divide; if they don’t succeed, p53 starts apoptosis. Apoptosis is basically a cell dying because they were “programmed” to die on command.
In cancer cells, p53 is usually missing or not working properly. If it isn’t working, the cell will be able to reproduce with the mutation. These new mutations can make cancer grow faster, spread, or be resistant to treatment. Side note: because cells can mutate to become resistant to treatments, the treatment needs to be relatively consistent.
Eluding the Immune System 👀 🕴
The immune system has three types of immunity: Non-specific/innate, specific/adaptive, and passive. We’ll focus on innate and adaptive. Everyone is born with innate immunity. Innate immunity responds immediately when it detects danger. It has a physical, chemical, and cellular level defense against cancer.
People are not born with adaptive immunity. Adaptive immunity is acquired from exposure. It doesn’t respond to dangers immediately, but its response lasts longer. Adaptive immunity rapidly increases the development of T-cells and B-cells. Although it can attack cancer, it can mess up and attack itself. This causes autoimmune diseases.
Can the immune system kill cancer cells? Yes. The immune system recognizes and attacks unknown microorganisms. Cancer cells are therefore frequently killed by the immune system, but the immune system eventually can’t keep up and is outsmarted by the cancer cells.
One more note on the immune system and how it works, then we’ll get into the nitty-gritty. Cytokines are proteins that regulate immune defense functions by acting as messengers between immune cells. They act on different cell targets in the immune system and can stimulate and stop growth. However, they go short distances in the body and have a short life. There are different types of cytokines including interleukins, interferons, colony-stimulating factors, and tumor necrosis factors.
Alright, on to becoming James Bond 🕵️♀️ and escaping the immune system. After the immune system loses its surveillance ability, tumor cells can pass unnoticed. They can escape because of several factors. Down-regulation of major histocompatibility class (MHC) — in this case, class I — makes the antigens unrecognizable. Since MHC finds unknown antigens, if it doesn’t work, it can’t find the foreign antigens — like cancer cells.
Tumor cells can also escape because there are fewer co-stimulatory signals. These signals are needed for the antigens to be seen. When the MHC molecule is lost or changed, it can decrease the co-stimulatory signals, which also means there are fewer of the 2nd signals, which are needed to activate the immune response.
Tumors can hide with immunosuppressive products. In addition, when tumors don’t give off inflammatory warning signals, it makes it easier to pass the immune system.
Lastly, tumor cells can avoid the immune system with antigenic modulation. In antigenic modulation, an antibody bonds two molecules together. This causes endocytosis, which lets the molecules degrade. Endocytosis is when a cell surrounds and accepts outside material — like an antigen — into it. When the cell accepts an antigen, the antigen can prevent the immune system from recognizing the tumorous cell as not a normal cell.
Effects of Avoiding the Immune System
Cancer can come back later on after being “cured” because the cells can escape the immune system. Usually, this happens with metastatic cancer. The cells that survived are called Latency Competent Cancer (LCCs) cells.
They can hide well because their protein is similar to stem cells, making stem cells and LCCs look alike. Stem cells are the “raw material,” meaning they are unspecialized but have the possibility of becoming specialized. Stem cells sometimes divide to repair tissues, which is part of why LCCs can divide and implant themselves in different locations.
I think of LCCs a little like spies, copying stem cells. So I have a quote about spies (and world dominance), then we’ll move ahead with LCCs.
Pose as a friend, work as a spy.
— Alexander Emmanuel
Some LCCs produce WNT inhibitor — a protein that stops cell division and slows the cell’s growth. This helps the LCCs go unnoticed, as their cell division is slowed or stopped.
You’re probably wondering, why doesn’t chemotherapy kill them? Isn’t that the purpose of chemotherapy? Chemotherapy only kills dividing cells. So, the LCCs that don’t divide — because they produce WNT inhibitors — can survive this treatment.
Because cancer could be latent, when someone gets an organ donation from someone else — who was “cured” of cancer — the person receiving the organ could develop cancer. Also, when someone gets an organ donation, they are given lots of anti-immune doses so the immune system will be weaker and accept the organ. This makes it easier for cancer to develop in the new person.
Cancer Research 👩🔬
History repeats itself endlessly for those who are unwilling to learn from the past.
— Leon Brown
With that being said, we will look at the current and past treatments for cancer.
First, let’s start with the current goal for metastatic cancer. Doctors mostly try to stop (or slow) the growth of cancer, improve the patient’s life quality, or try to prolong their life. Metastatic cancer is mostly incurable, so doctors primarily focus on what’s best for the rest of the patient’s life.
Now onto treatments… Angiogenesis inhibiting therapies stop blood vessels from growing towards the tumors by blocking the ability to produce new blood vessels. This prevents the tumor from growing, as there isn’t a supply of nutrients or oxygen anymore.
Immunotherapy can use vaccines to “train” immune cells to destroy cancerous cells. It uses interleukins to increase the immune system’s defense against cancer. However, immunotherapy is less effective than other therapies, and deadly side effects are possible. Therefore, it is usually a last resort to use this.
Checkpoint inhibitors stop the checkpoint proteins from connecting with other proteins. Checkpoint proteins prevent the immune system from having too strong of a response. This can result in T-cells not being able to kill cancer cells. The inhibition of checkpoint proteins lets immune cells find and destroy cancer cells/tumors.
CAR-T immunotherapy treats blood cancer. In this therapy, scientists remove T-cells and by using an inactive virus, they genetically engineer the T-cells to create chimeric antigen receptors. This lets the T-cells recognize and bind with proteins/antigens on tumor cells.
Gene therapy treatments are where doctors remove the mutated genetic material and replace it with healthy material. They insert genetically modified genes into white blood cells, which gives the blood cells a better chance at finding and fighting tumors. These modified genes can reactivate the self-destruct feature in cancer cells.
Cancer treatments sometimes use viruses that can destroy the cell or alter it. One virus that kills cancer gets 1 strand of DNA — a.k.a. RNA — in between the DNA helix (shown to the left). This jams the DNA and prevents it from functioning.
CRISPR is starting to be used and has great potential for the future. CRISPR reprograms immune cells to find and attack tumors. To get into more detail, microbes save parts of an antigen’s DNA as smaller sections called CRISPERs. If the antigen tries to attack again, the DNA sections help Cas — an enzyme — destroy the antigen’s DNA.
There are different ways scientists use CRISPR. One way is where they “delete” 2 genes in patients’ T-cells, making the T-cells better at fighting cancer. One of the genes they remove makes checkpoint molecules — specifically PD-1. PD-1 is a protein on T-cells. Cancer uses PD-1 to stop the immune system and keep the immune system in control. The other gene they remove is the receptor that is used to detect dangers. This would be replaced with a redesigned receptor that is steered towards certain tumors.
AI is starting to make headway in the cancer world. It is being used to detect cancer and tumors that doctors might miss. That being said, it is more of a second opinion because it isn’t fully effective.
