Since the early 1700s, cancer has been a major topic of debate, discussion, and innovation. From the development of anesthesia to the accidental discovery of applying radiation on cancer, our understanding, and treatment of cancer have revolutionized the impact of this disease.
This tremendous advancement has enabled nearly 17 million people in the US to fully recovered from cancer just in 2019 alone.
So… the question remains: how did we get here?
Let’s cover the basics
As a result of mutations, certain cells do not abide by the physical and chemical factors which control their division and survival. Instead, they continue to divide rapidly and survive where they are not supposed to. The result of this abnormal growth in different parts of the body is called cancer, and a tumor is a mass of these mutated cells.
There are two types of tumors: benign and malignant. Benign tumors are made up of excess cells that do not travel, metastasize, to other parts of the body but instead stay together in their area of origin not growing or growing slightly. This first-growth is called “carcinoma in situ” (CIS).
Benign tumors are generally not considered life-threatening.
When these benign tumors metastasize, they migrate through structures such as blood or lymph vessels and multiply in other parts of the body, forming a malignant tumor.
In order for malignant tumors to grow away from the original mass, cancerous cells generate chemical stimulants that hijack the cell division cycle and stimulate tumoral angiogenesis.
Angiogenesis is a process that regulated the growth of new blood vessels needed to spread blood supply and nutrients to tissues in the body. When cancer cells form, they send to signal normal tissues around it to form many vessels around it. As a result of the abundance of resources, cancer cells have enough nutrition to grow.
Studies are showing that the VEGF family of growth factors and receptor tyrosine kinases are found in large amounts in tumor cells, indicating that they play a role in angiogenesis. It is hypothesized that this is because hypoxia, a situation where part of the tumor tissues has low levels of oxygen as a result of its rapid growth, the cell increases the expression of VEGF which leads to a series of reactions that create new blood vessels. Along with this, metastatic tumors also influence other elements of the extracellular matrix (ECM), the environment around these cells, which help maintain cancer cells.
Malignant tumors are considered cancerous and dangerous.
In order to properly understand each cancer, scientists classify each tumor based on the organ they originated from and the progression of the metastasis (ranging from stage 1 to 4). Given the diversity of cancers, categorization is key to targeting them.
So…if cancer is so researched, why haven’t we found a cure yet?
Think about it like this: Imagine you are playing a carnival game and your goal was to hit a color-changing, fast-moving, shape-shifting cartoon without hitting any other of the surrounding moving objects.
It seems nearly impossible right! This is exactly what scientists attempting to find a cure are trying to do.
No, cancer’s don’t change color but most types, other than carcinomas, or melanomas, undergo clonal heterogeneity.
When they metastasize, the parts of the original tumor that migrate have slight mutations that lead to a “subclone” that are drastically different from the original.
This is why scientists are trying to generate medicine that is specific to the type and mutations of each patient.
And, no, cancers don’t shapeshift but, they are very unpredictable. The most common way of studying cancer occurs in an in vitro environment, meaning outside of the body, and most commonly on cancer cell lines. However, cancer cells behave in a far more complex way. Their behavior is polar to the status quo of healthy cells and a treatment that might work in a lab might prove faulty in the body of the patient.
Though scientists are far from hitting the target, many effective treatment methods have been developed to minimize the spread of cancer.
Current Common Treatment Methods
There are two main types of treatment: primary, adjuvant, and palliative.
Primary treatment is in charge of eliminating cancer cells; adjuvant treatment is a type of cancer treatment that gets rid of any of the leftover cancer cells that remain after the first treatment in order to assure that no trace of cancer remains.
On the other hand, palliative treatment is the type of treatment that helps alleviate any of the side effects as a result of cancer.
A patient’s treatment plan is personalized to best fit them and most likely contains a combination of treatment methods, with almost always a form of adjuvant treatment.
So what are the most common current treatments?
Surgery can be used to state the type of cancer and its level of advancement. Different types of surgeries have different roles in the treatment process.
A biopsy is a procedure that takes a sample of cells of the growth inside your body in order to run tests to develop a determine the type of tumor and its severity. Before choosing to do a surgical biopsy, physicians check for less invasive ways of extraction depending on that particular type of cancer.
Tumor removal Impact:
The goal of this type of invasive procedure is to remove as much cancer as possible. During this procedure, physicians take a rim of extra tissue around it, called a margin, in order to ensure that all of the tumors are removed. Surgical tumor removal is the most used cancer treatment for brain and spinal cord tumors.
In certain cases, surgery can be used to repair damaged areas, such as bones, done by cancerous cells after the tumor is removed.
Preventive surgery is performed to lower or eliminate the risk of getting cancer. For example, for women whose families have a history of breast or ovarian cancer, they choose to get their breasts or ovaries removed before any sign of cancer is present in order to remove its possible threat.
As a cell progresses through the cell cycle, it has to pass checkpoints, pausing points where the cell awaits for a protein signal which ensures that everything in the process is going as it should be and the cell can move on to its next stage(ex: the cell has all the organelles, if the cell is the appropriate size, if the DNA is replicated correctly).
Cancer cells do not follow the same process. Some types move past the checkpoints without the need for growth factors; other types synthesize their own growth factors in order to pass the checkpoints. Chemotherapy is a treatment that uses drugs, in the form of pills or injections, to target cancer cells at specific times during the cell cycle using cytotoxic agents (meaning toxic (-toxic)to cells (cyto-)).
These drugs cause damage to all cells, even healthy ones, but their full effect is only applied to cancerous cells.
Because of their rapid reproduction, cancerous cells take in larger amounts of these agents, causing their DNA to get so damaged that the cell is destroyed. Unfortunately, this drug has a similar effect on naturally rapidly dividing cells such as hair follicles and gastrointestinal lining. This is why patients undergoing chemotherapy experience symptoms such as hair loss, nausea, and fatigue. After the round of therapy is over, these damaged normal cells begin to renew and function as usual.
Examples of drugs used in chemotherapy:
Alkylating agents are used to damaging the DNA of the cell. This prevents cancer cells from reproducing and making copies of itself.
Anti-tumor antibiotics are chemotherapy drugs used to change the DNA of a cancerous cell to keep it from dividing.
On the other hand, anthracyclines are an example of anti-tumor antibiotics that inhibit enzymes that help replicate DNA during the cell cycle.
Radiation therapy uses high beams of energy, radiation, to target cancer cells. Radiation damages a cell’s DNA by creating breaks in a DNA sequence and, as a result, prohibiting cancerous cells from replicating. Radiation therapy is local, meaning it only targets the general area of the tumor, and it is often as an adjuvant treatment.
There are three types of radiation: external, internal, and synthetic.
External radiation is supplied from an external force such as linear accelerators or cobalt machines. It uses high beams of energy such as X- rays and radioactive substances, to damage and shrink the cancerous tumor.
Internal radiation (brachytherapy) is conducted by placing a radioactive temporary or permanent implant near or inside the tumor; this is to protect nearby cells and limit their exposure to radiation. Unlike external radiation, internal radiation uses small doses of higher radiation in a specific area.
Synthetic radiation is a branch of radiation in which the patient takes in radioactive material by mouth or vein that travels using the blood system. They are often attached to an antibody which helps them detect, attach to cancer cells, and release radiation.
Bone marrow transplant
Bone marrow transplant is a procedure that replaces damaged bone marrow, either from cancer or a treatment such as chemotherapy, or bone marrow dominated by cancerous cells with a new one given up from a donor.
By doing so, the patient has new stem cells that can make healthy blood cells again and possibly detect any cancer left better. In some cases, the patient's body identifies that the cells in the bone marrow are foreign and begins to attack them; this is called graft rejection.
Immunotherapy is a cancer treatment that aims to use the patient’s immune system to fight cancer cells. As of now, two main methods are being explored: the stimulation of the patients’ immune system or contribution of man made-components to order to detect and fight cancer cells.
The immune system requires a very specific balance of conditions to function properly. Interfering risks the immune system attacking normal cells just as aggressively as cancer cells.
T cells are a type of white blood cell that is in charge of destroying threats to the immune system. Regulatory T cells (TREGS) control the immune response and are in charge of inactivating T-cells. This is to prevent them from destroying healthy cells they encounter. When T-cells bind to the tumor, cancer cells take advantage of this system and turn them “off”. Studies have shown that IL-10 and IL-13 are examples of TREGS. These together have seen to the protein BLIMP1 which generates a mass of inhibitory cells on the surface of T-cells which makes them less sensitive to detecting cancer cells. This, however, is just one of the possible reasons behind the deactivation of T-cells.
Checkpoint inhibitors are drugs that aim to off these factors that affect T-cells. The majority of these drugs are being researched.
Another blooming aspect of immunotherapy is T-cell therapy which aims to help the immune system detect cancerous cells. This therapy is explained below.
Though these treatments have immensely increased recovery success, they are far from perfect. This is why new methods are constantly being researched to best eradicate this disease.
This August, the FDA has approved two blood tests that profile the tumor.
One of the biggest problems when finding the proper cancer treatment is that cancer has so many types of mutations and specific treatments, referred to as targeted therapies (explained below), are only effective on specific mutations.
The goal of these tests is to identify mutations in the traces of tumoral genetic material in the blood. The term coined for this type of sequencing is genomic profiling or tumoral sequencing. These types of liquid biopsies could be key to precision medicine which aims for a personalized treatment based on the specific mutation of a patient’s tumor.
Meanwhile, other types of liquid biopsies are focused on early detection. Most biopsies take place invasively or once the tumor has developed. Liquid biopsies allow for a non-invasive and easy alternative method which is especially helpful for monitoring patients who might be more genetically predisposed to develop cancer or have already had cancer. Unfortunately, the latter is far from being available in the market but is being researched and studied.
Targeted therapy is a special branch of immunotherapy and chemotherapy that aims to utilize the patient's own immune system to fight cancer.
Think about it like this… if a castle was being attacked, wouldn’t you want your on-field, most knowledgeable, most strong worriers to fight the invaders than wait for external weak help?
Targeted therapy aims to enable our immune system to fight cancer itself. Targeted therapy is different from traditional chemotherapy in the sense that it specifically targets cancer cells. CAR-T therapy is a type that has shown the most progressivity and success in clinical trials.
So.. how does it all work?
CAR-T therapy uses Adoptive Cell Transfer (ACT), a commonly used technique used in immunotherapy that collects a patient's immune system. In the case of CAR-T, ACT is used to collect T cells. T cells are then genetically engineered to produce receptors called chimeric antigen receptors (CARs) that help T cells recognize and attach to antigens, identifying proteins, on tumoral cells, and, therefore, attack them.
The promising impacts of CAR-T therapy have started to be seen. This method has been largely tested on patients with acute lymphoblastic leukemia (ALL) which is the most prevalent among children and one of the hardest to successfully treat. However, when an early study put this therapy to the test, it was shown that 27 out of 30 young patients became cancer-free.
Nevertheless, many hurdles remain in the way. Currently, this treatment is mostly used for blood cancers, a lot of progress is being made towards targeting solid tumors. Furthermore, more research needs to be done to understand and lower the probability of serious side effects, and most importantly, to increase the effectiveness of this treatment.
Much research is also being done on identifying and targeting cancer stimulating proteins, tumor angiogenesis, genetic components (ex: BRAF gene), and even the impact of the bacterial microbiome on the immune system.
But if so much research is being done, why are relatively few treatment methods being approved?
The FDA and the drug discovery pipeline is rigorous and requires much testing in order to assure that these treatments are effective and safe. This also means that 86% of drugs fail clinical trials alone. However, it doesn’t mean that the research we are doing is all futile. 14% of drugs do successfully pass FDA approval and many promising treatments are currently in the final stages of clinical trials.
The pitfall for many cancer treatments undergoing trials is that the drug behaves differently in an in-vitro environment than in the body; this conflict of models continues to remain a considerable roadblock.
The key is to rethink our route and come up with creative solutions that allow us to surpass the challenges we currently face.
A Glimmer Of Hope
Though cancer is complex, so are the emerging ideas that will counteract it. We now know more about cancer than we have ever had. And most importantly, we are putting more of our ideas to the test than ever before. Innovation and creativity will continue to drive research and defeat cancer.
This is just the beginning.
- American Cancer Society | Information and Resources about for Cancer: Breast, Colon, Lung, Prostate, Skin
*Other resources used have been embedded in the text.*