Will 3D-printing revolutionize the treatment of Cancer around the globe?
M y first interaction with the cancer world was when I got to know more about what some of my family members went through. My cousin who was in his twenties, a man in the shining years of life, died because of leukemia which advanced within a short amount of time which happened before my birth into this world. My grandfather also died before I was born. He had stage 4 lung cancer, probably as a result of smoking and a late diagnosis along with passive prevention.
But is it only because of environmental changes which you may or may not influence? This is something I began to doubt after seeing my uncle being diagnosed with an aggressive form of cancer too. After quite some time, my uncle's granddaughter who's the little daughter of my cousin, also got diagnosed with cancer (lymphoma). My uncle's daughter, the mother of my little cousin, also got diagnosed with cancer, to be precise a rare version. This rings huge alarm bells screaming: Is the disease of cancer hereditary in our family? Is this hereditary curse following us for the rest of our lives? What can we do about this?
Some of you are probably thinking: "Here's another sad story trying to convince us of some nonsense using great words." This is not why I am writing this article. The reason why I'm writing an article is because of my passion for cancer. Now you're probably wondering: "What makes a 17-year-old passionate about cancer?" Let me explain.
Cancer is a disease that has been an enemy for many people around the globe. I want to help make a change, even if it's small due to my own experiences with cancer. Knowing I can do something, like gain knowledge about what happens before cancer, during cancer, and after cancer exists or has gone away, makes me more vulnerable (in a good way) for brainstorming which could lead to an actual result or progress in the field of cancer treatment. Nowadays, many technologies can provide an aid to help cancer become more treatable or curable. But, why is it so hard to cure cancer like they always say on social media? That's something which we'll discuss later.
To understand cancer, we have to understand genetics. That's why we're going to go through some basic genetic knowledge.
Genetics
O ur body cells have chromosomes (©) in the nucleoplasm in the nucleus (= the center of a cell). 1 body cell contains 46 chromosomes. 1 genital cell contains 23 chromosomes. If a formula had to be made it would be as follows: ©genitals = ½ × ©body or ©body = ©genitals × 2. Chromosomes are long wires full of information with genes and alleles specifying what you are and what you possess genetically or have inherited from your mother and/or father a.k.a. the genotype. The genotype exists when the nucleus of the sperm cell or spermatocyte has merged with the nucleus of the egg cell or oöcyte, where the formula proves that ©child = ©mother(egg) + ©father = 23 + 23 = 46 Chromosomes (Embryo). This genetic information in the chromosome is also known as DNA and all DNA molecules in a cell are called the genome. DNA regulates all functions within a cell. Now our human body consists of 37,2 trillion cells which is an average since this varies from human to human according to National Geographic. DNA contains deoxyribose (carbs), proteins (receptors), and enzymes that help support the functioning of the body.
DNA & RNA
A DNA molecule has double strands, but how do these double helixes' exist? DNA consists of 4 nuclease bases: Adenine (A), Thymine (T), Cytosine (C), and Guanine (G). Adenine 'bonds' with Thymine and Cytosine connects with Guanine, and vice versa for both of the two pairs. If one side of the strand (s1) has ACTGCAT, then the other strand (s2) has TGACGTA. Because of the opposite nuclease bases in s2 which bind to the ones in s1, the double strands are being created by connecting them. This order of DNA pairing is also called DNA sequencing. Also, one stranded side or a "single-helix" with genetic info is what we call RNA.
The function of DNA and the mistakes it makes
We talked earlier about what DNA is and what names we have for many things, but what tasks does it have? Well, the most important ones are cell division and apoptosis (= by the body programmed cell death) which are forms of self-regulation. When an error happens within the sequence of DNA, immune cells in our body kill it to prevent issues. When a (sudden) change in the DNA sequence or genotype has happened, we call it a mutation. A mutation could be anything, a change of eye color, a different growth development, etc. When the mutation means no apoptosis in the body, that's when we think of a tumor. There are two types of tumors: benign tumors and malignant tumors. Benign tumors are tumors that contain non-cancerous cells that won't spread to other cavities or places in the body. Malignant tumors are cancerous and will spread through and to other tissues (lymph nodes) and organs.
https://my.clevelandclinic.org/health/diseases/22319-malignant-neoplasm
Once a person has a malignant tumor and it is found, it will be diagnosed as cancer. However, that’s not all. This "cancer" has stages, meaning how advanced your cancer is. These stages start at stage 0 and end at stage 4 with 1 being good and 4 being the worst. Here you can see an overview of the stages of breast cancer which was made by Memorial Sloan Kettering Cancer Center (MSKCC). The stages of cancer are all the same, even if the cancer is different.
A s you already might know, a mass or tumor is detected on a CT scan which uses Computer Tomography to take a fast series of X-ray pictures that are put together to create a structure that makes body parts and tissues clear to look at. An MRI can also detect a mass using strong magnetic fields to take pictures of a part of the body that you’re concentrating on. The MRI-Scan is only used if it can pick up on things that a CT scan can’t pick up on which is used in rare instances. Surgery will most likely follow after a scan to do a biopsy which is surgically removing the tissue (as much as you can) to determine whether it’s benign or not. When this tissue is being examined by a pathologist, there is a checklist to go through a.k.a. 'the hallmarks-list’.
There are 10 main hallmarks or characteristics of cancer:
1. Growth signal autonomy: Cancer cells divide without needing the signals telling a cell to divide.
2. Insensitivity to growth inhibitory signals: Malignant tumor cells ignore the signals to stop cell division, making the tumor grow more.
3. Evasion of apoptosis: When there's a lot of damage to the DNA or abnormalities, a programmed cell death kicks in. The abnormalities are destroyed in normal cells. However, in malicious cells, the damaged cells continue to divide and ignore the apoptosis signals.
4. Reproductive potential not limited by telomeres: A telomere is the end of the chromosome. Cancer cells maintain the length of the telomeres, even though normal cells arrest further division once the telomeres reach a specific length.
5. Sustained angiogenesis: Most cancers require the growth of new blood vessels into the tumor. Normal angiogenesis is regulated by both inhibitory and stimulatory signals not required in cancer cells.
6. Tissue invasion and metastasis: Normal cells generally don't get transported (except in embryo development). Cancer cells invade other tissues including vital organs.
7. Deregulated metabolic pathways: Cancer cells use an abnormal metabolism to satisfy a high demand for energy and nutrients e.g. glucose and oxygen.
8. Evasion of the immune system: Cancer cells can hide from the immune system, because they can detect signals that are being sent by immune cells, like T-cells which are a sort of white cell.
9. Chromosomal instability: Severe chromosomal abnormalities are found in most cancers.
10. Inflammation: Local chronic inflammation is associated with many types of cancer since it suppresses the immune system causing vulnerability to suffer from a medical issue like an infection or virus.
Detection and diagnostic imaging
What happens during cancer is the fact that it ignores all signals that keep the body from maintaining good homeostasis which is a dynamic balance that is regulated by a control circuit keeping e.g. glucose and oxygen levels in the blood at their standard value so that the body can function in an orderly fashion. In cancer these glucose levels and oxygen levels are pretty low because malignant tumors feed themselves with sugars and lots of oxygen for the cells to stay alive with the help of angiogenesis, the creation of blood vessels. That’s why you can see a high-concentration of glucose in regions of the body on a PET-scan which could indicate that there is a mass or a tumor present and what stage the cancer has got to reach.
Compared to all kinds of scans, a PET-scan is the best scan you can get to determine the severity of your cancer. It highlights the metabolic activity that is being stimulated by mitochondria in our body cells. For that to happen lots of glucose and oxygen are necessary to turn that into water and carbon dioxide so that the energy gets released in the form of ATP e.g. and water like our sweat. A CT-scan, MRI scan, or X-ray would not be able to highlight the abnormalities as well as it should. Below you can see two images that give you a simple analysis regarding the differences between the different scans.
For detecting lymphoma, sometimes an ultrasound will be used. This ultrasonography uses high frequency sound waves that are translated into pictures. A vast majority of people are familiar with using an ultrasound for prenatal care and to observe the fetus as it develops. This is solid proof that ultrasounds are safe, even when women are going through cancers like lymphoma and getting themselves checked out by the physician with or without pregnancy.
Location of cancers in the body and the most deadly types of cancer
Many cancers exist. Each one is in a different place in the body. We can categorize which cancers are the deadliest and which aren’t. What makes them so hard to treat? Better question: Why are they the deadliest forms of cancer? or Why are they not the deadliest cancers?
The deadliest cancers are being fought by various companies in the EU which can support countries outside of Europe. There are 8 deadliest cancers: esophageal cancer, pancreatic cancer, stomach cancer, etc. Cancer reprograms their metabolism and starts creating a Warburg-Effect which is transferring a huge amount of glucose to the malignant cells and because of an anaerobic environment along with having a high amount of lactate, it results in the cancer staying alive, hence why patients experience fatigue, exhaustion and weight loss depriving the muscles from growing and as a result being broken down.
We know that cancers mostly kill, but also don’t always kill a person resulting in remission or the “time of death being called" which is horrible of course. But, that doesn’t have to be the case.
There are multiple treatments which I'll explain to you since these are the most known options for treating cancer:
1. Chemotherapy: The use of drugs - pure poison - to destroy cancer cells. However, it also destroys the good cells in the body making someone more susceptible to viruses, bacteria, and much more. This state is something we call being immunocompromised.
2. Immunotherapy: Administering cells that support the white blood cells to help your body fight the natural defenses to the cancer.
3. CRISPR-CAS: Detecting the mutation or 'fault' in the gene, cutting the fault out, and replacing it with a good new part of a gene.
4. Hormone-Therapy: Administering, removing, or blocking certain hormones in the body to make the cancer weaker and more vulnerable to other treatments.
5. Targeted Therapy: Treatments target and disable genes and/or proteins that are found in cancer cells that need to grow. This can treat several types of cancers.
6. Radiation: Using beams of intense energy to kill cancer cells instantly. Oftentimes, X-rays are used. A new development is proton radiation.
7. Stem cells: Cells promote the repair response of diseased, dysfunctional, or injured tissue using stem cells or their derivatives known as regenerative medicine.
8. Surgery: Resection of the tumor as much as you can or fully along with operative-lasering and resection.
In rare cases like metastasis, flushing the body with chemo for a few hours is also recommended. Although it does increase the risk of complications and even death. It is a surgery with a technique known as the HIPEC-approach. It gives a patient an option and opportunity to fight as much as they can and still have a higher chance at curing their cancer instead of doing nothing at all. The age factor plays a huge role in such decision making, however.
9. Bone marrow transplant: This process entails the extraction of stem cells typically located in the bone marrow, followed by their purification, and subsequently administering them back to either the original donor (the patient) or another recipient.
As you can see nowadays, there are many treatments to help cancer patients fight the malicious disease. Here’s an image of the success rate for each of the cancer treatments as explained above.
Strategic treatment planning & determining a direct approach
Certain cancers require an invasive treatment approach because these tumours are more aggressive, meaning that an oxygen deficiency, low pH levels, and lack of nutrients kill cells. Those cells do survive a.k.a. "stressed cells" tend to react aggressively. First, they go into a resting phase, which is when they’re immune to treatments like chemo-, radio- and Immunotherapy. At this exact moment, fat droplets are used as fuel to keep the cells alive. Once it stops being in a resting phase, it will grow and spread itself throughout the body via tissues, organs, and/or bodily fluids. It could also happen because the cancer was discovered in a late stage (stage III or stage IV) and is hard to treat with medications only. This leads to metastasis.
(B) The connection between arteries and venous blood vessels of healthy tissues, and the disordered connection in tumor tissues.
Treatments that would more likely be successful for the aggressive course would be a mix of treatments: surgery, high dose of chemo- and Immunotherapy along with strong radiation and medications should give you the expected good result. However, that is not always the case. The average cycle time for the division of normal cells and cancer cells is 48 hours. The reason why the tumor becomes so big is because it creates additional cells rather than replacing them and breaking the previous cells down. Using lower dosages or weaker forms of radiation would not have an effective outcome.
In less deadly cancers, the best thing to do is to look at whether you can do a resection of the early stage (stage 0, stage I, or stage II) tumor. When that's done, you can also look at how to combine that with chemo- and Immunotherapy to make sure and determine whether curing them is still possible. In stage 0 or I, that's very likely to happen and is still a very good stage to save someone with all confidence of remission. In stage II it is also more likely, but in some cases, it is almost in stage III but not yet and therefore categorized as stage II. That's when things change because you'll have to eventually make sure that you're going in the direction of stage 0 which is similar to walking backward from something bad you see to save yourself.
Imagine being a pathologist in a lab wanting to test multiple treatments on copy’s of something to recognize which therapy is best, but you have nothing that can help you. Let me introduce 3D-bioprinting to you which uses bio-ink, like real cells from e.g. a biopsy to determine what characteristics cancer has and what treatments may be optional for use. Once we know what the code is for the characteristic based on the genetic information, we can put this in a computer with an algorithm to make sure that the exact duplicate or replicate can be printed with real cells, the bio-ink. Once multiple duplicates have been printed, you can test on every one of them what effect a treatment has on them. So how does that one tumor react to chemotherapy, gene-editing (CRISPR), immunotherapy, etc. That way we can find the best solution and treatment options for a specific cancer to cure it and that way the patient doesn’t have to suffer so much because they normally try out treatments by making the patient go through them themselves. This can be done for each patient individually and adjusted or individualized for each person. In this video down below it goes deeper into the specifics in this new and developping field of science and how it works giving a simple and understandable glimpse into how 3D-bioprinting demonstrates its functionality.
Helping find a treatment prior to starting catheterization, IV-infused treatments or invasive procedures by replicating cancer cells from a biopsy and trying different treatments on them for each replica. That way a patient and human being doesn’t have to suffer as much. Printing them with real cells (bio-ink) to get these biological structures to form. This can be applied to each individual’s cancer and its characteristics that can be detected through algorithms where AI starts to play a role as well. A few professionals have already talked about this on Pubmed | National Library of Medicine | National Centre for Biotechnology information.
Personalized medicine
And medication wise, 3D-printing or Bioprinting can help with getting and creating drugs which are best for the patient. Students and professionals in India talk about why this personalized medicine approach can also be very helpful and have talked about it in an article here. And if there's a known combination of drugs which are effective, then you can make it one capsule or pill instead. Also, if you combine drugs all together and then put in certain time-intervals which are triggered after a reaction of a chemical has finished so that the effectiveness of a so called (trial) drug can be the most effective thing.
As you can see in the diagram we have got 3 kinds of medications, we call them drug A, B and C. Let’s say drug C is the mix of the combined drugs all together. After some time it will start to kick in and eventually the concentration of drug C will become lower and almost done during interval time = 0 to time = 1. Then drug A that gets released will continue to increase and get into the bloodstream to be broken down, released and processed which takes a lot longer than drug A or B during time = 2. Once that has happened and finished, drug B will start to kick in and eventually the content of the drug will become less and less until it has fully reacted and interacted with the specific chemical process. This happens during time = 3.
Do note:
- Every number stands for the interval.
- Time means the amount of existence that is left of something.
- Concentration means the drug of A, B and/or C.
- The velocity of how fast the chemical process happens is the difference in concentration divided by the difference in time (interval) in which the chemical reaction takes place.
The diagram can be used to determine values of the concentration and time to be used in this formula and calculate the exact answer as to how fast it goes. The “Average Rate” or velocity of the chemical reaction is expressed in mol/L/s or M/s, because mol/L=M. It can also be expressed with different units depending on what the number is that you’re getting. Therefore, it is possible that the “Average Rate” has the unit of g/L/s or kg/m³/s which could mean that the density (ρ) divided by the time is the average rate which is theoritically possible but practicly speaking, not. The “Average Rate” is always positive, even if the difference in concentration is negative.
After patients have gone through many treatments to possibly cure their cancer or help them with having a quality of life is a daily non-stop battle which never ends. Doctors prescribe various medications: a few for the treatment of cancer and the others as a supressor for the side-effects which causes cancer patients to feel like they are living in messed-up misery. This is another reason why 3D-printing is the best option and most effective since it can help with manufacturing medications with specific time intervals when certain compartements of the customized drug gets released. If we can make one pill or capsule which is perfect for the patient and can be customized, then that is what needs to happen. Improving the quality of life will help the patient heal mentally and physically a lot better which is something Sanofi strives to do.
3D-printers can be programmed by a computer to read the create and read the characteristics of multiple drugs and see how it forms as a whole. Although, it is the professionals who have to determine for each patient based on their medical history how high or low the dosage and how long or short intervals for the “chain-reaction” must be in order for the patient to experience change.
Because of the “domino-effect” the interval-approach has in personalized medicine for cancer, it can release drugs in a specific order. For example, on time = 0 to time = 1 a chemo-pill is working and on time = 2 the content of a nausea-supressing medication is working and on time = 3 the immune-drugs will kick in to help keeping the body from environmental disturbances like parasites, virusses etc. One reacts after another time after time until it stops. The intervals can be increased and/or decreased if necessary by pharmacists and lab-workers who would work closely with medical professionals and manufacturers, giving the patient more control over their treatment in the future.
A company that currently works on this new technique is CELLINK. They also work on various other disciplines like personalized medicine which can be used for clinical trials potentially leading to a future revolution of treating illnesses. This can help multiple branches in the field of healthcare and outside of it. The food industry for example provides a proactive way of treatment also known as prevention. They are applying bioprinting to cancer in a effective way which makes treatment a lot better. They have also been working on organ printing which also means that replica’s of cancers can be made with the help of a CELLINK 3D-Bioprinter.
Economics within the cancer-industry
According to medicalnewstoday a full round of chemotherapy is almost around $27,000 USD. The costs for Immunotherapy is for "a full course of experimental cancer immunotherapy in the $30,000 USD to $40,000 USD range", which Biotheraphy International stated. Healio has said that it costs $13,358.37 USD for a 6-week conventional radiation treatments which is 1 round of radiation. 3D-printing depending on what it is used for can vary from $3 USD to thousands and hundreds of thousands of dollars USD. What is clear is that the cost for printing for CELLINK is very expensive but that the entry for research costs were lowered in 2015 by investing in more expensive equipment. Will this give us more opportunities in the future which is now? However, depending on the funding, sponsorship and your insurance policy … it is still possible for it to become cheaper. This is something we’ll have to fight throughout the new developments that will exist in the future.
We can see that the known treatments at this current time are not specific enough for a patient themselves leaving them in distress medically, mentally and financially. This way of printing is to some extent cheaper than any other treatments at the moment. There's a company with a website called excedr, helping you to save money and time for the use of bioprinting and gives you multiple manufacturers who are professionals in 3D-printing. This could help with time management and finance solutions for healthcare institutions, investors and patrons.
My opinion
What needs to happen is for patients to get access to these kind of companies working in 3D-bioprinting for cancer purposes, like CELLINK. The financial burden for companies themselves is already huge. A new insurance policy and economic reform for the field of healthcare should be started, using the new ways of financial platforms like blockchain. Collaborating with economic professionals who are willing to truly make a positive and effective change to make sure that people benefit of the advantages there would be once the solution would’ve been put to practice and on trial to predict the future’s prognosis in cancer treatment. I believe that if we support this new technology in letting it become the new treatment option for various illnesses and fund it properly with the right attire and people, then that is what needs to happen! We’re not just talking about one discipline here, it’s about thousands and billions of people who can benefit from this! Save lives now, not tomorrow!
