Currently used Cancer-Therapies

Cancer poses a threat to the whole human population on earth. Therefore, it is a topic that concerns every single one of us and should be known better. It is widely known, that cancer is caused by the uncontrolled growth of parts of tissues that results in tumors. The cancer cells are no longer able to control their cell cycle and never stop dividing. They do not recognize the borders of their tissue anymore and keep growing until some of them even leave the tumor and travel through blood- and lymphatic vessels to cause tumors to form in the entire body. If this happens, the disastrous process is about to reach its end: The patient is almost surely doomed.

But how and why does this happen? Why are they able to do this?

When cells divide, they have to copy everything functional inside them, this also includes the DNA. Every time the DNA gets duplicated, the polymerase has to synthesize new strands of it, and unfortunately, it does not work perfectly and sometimes makes mistakes.

In normal cases, these mistakes get recognized and eliminated by other control mechanisms, but they are not perfect either and thus, it may happen that falsely replicated DNA strands will not get corrected.
This may result in the damaging of important mechanisms of the cell division and also could delete the control over it. As a result, the cell will divide without stopping and keep mutating. If they are not recognized by the immune system, there are almost no hurdles left for the cancer to successfully grow, metastase and kill the patient.

Until now, there have been many desperate attempts to stop this disease through the invention of various therapies. Sadly, none of them can promise a guaranteed cure for this disastrous illness that causes so much misery. In many cases, they even make the quality of the patient’s living much worse than the cancer does itself because of the horrendous side effects. In many cases, the patient may even die because of them instead of the consequences of the cancer, making it even harder for the patient and his/her suffering loved ones.

Even in the most often used therapies such as chemotherapy and surgical removement result in severe side effects and pain. Vomiting, diarrhea and a heavily weakened immune system are only a few of the disastrous consequences of common cancer therapies.

But there can happen much worse things to the patient: Even if the therapy might result in the elimination of the cancer, it is common that second cancers such as leukemia occur a few years after the original treatment, that lets the patient experience these horrific moments of his/her live once more.
Also, some therapies can cause the patient to become infertile, destroying the vision of a happy family.

All in all, the recent cancer therapies leave much to be desired. In the following, you can experience more about the most common recent therapies and their way of functioning, as well as their many downsides.

Chemo- Therapy

One of the most common known therapies to fight cancer is Chemo-Therapy (CT). In CT the patient is treated with chemicals that are also know as cytostatic drugs. Cytostatic drugs works like cytotoxins and their main function is to inhibit and ideally stop cancer growths and therefore reduce the cancer in size. It is one of the most used therapies to combat cancer and is often used in addition to other Therapies like Radiation-Therapy.

The most frequently used CT are FOLFOX, that is used almost strictly in patients with advanced, metastatic colorectal cancer and CHOP that is used to treat non Hodgkin lymphoma. In both Therapies a wide range of chemicals are used to fight the cancer. But the chemicals that are used do not only affect the cancer. They attack all fast proliferating cells and not only the cancerous ones by targeting the mitosis and the distribution of chromosomes. Under the most common side effects of CT are many of those people associate with cancer:

• Hair loss
• Nausea
• Fatigue
• Nerve tingling
• Fall in number of blood cells a weakened immune system
• Diarrhoea

But there are also many possible long-time side effects caused by CT:

• Infertility
• Second cancer
• Heart disease

Radiation- Therapy

High-energy radiation can damage tumor cells efficiently enough to kill them. Healthy cells do not react as sensitive: With their repair mechanisms, they are able to fix the damage the radiation caused. The tumor cells no longer have these repair mechanisms at command, they can no longer defend themselves and die.

Especially, free radicals such as oxygen ions form and damage the DNA of the tumor cells. Enzymes and other molecules that are involved in the fast proliferation of the cancer are damaged by them as well. Then, after being damaged to a certain point, the body detects them as damaged cells and eliminates them specifically through apoptosis.
Moreover, with today’s technology, the radiation can be carefully directed to the tumor, so that side effects decreased over the time with the development of technology.

Instead of giving the whole radiation dose at one point, the patient is treated with several smaller “fractions” or “portions” of the planned total radiation. This technique serves the purpose to give the neighboring tissue enough time to regenerate and to replace the cancerous tissue with a kind of “scar”.

Moreover, the risk of receiving a lasting aftermath does not increase too much. But this therapy also has its downsides: Radiation damages many aspects of a living cell, for example the DNA and important metabolic pathways, even in healthy cells. If the radiation is given in doses that are too high, so called radionecrosis may develop. In that case, various important tissues die and degenerate. However, it is very difficult to detect the amount of radiation a tissue can bear without taking damage. For example, blood- and immune cells, hair roots, the kidneys, the lung and even the eyes are particularly sensitive. Because of the DNA-damaging nature of radiation, the possibility of developing a second cancer ten to twenty years after the treatment increases.

Immune- Therapies

Immune Therapies are a quite new way to help people with cancer. For many years cancer patients were treated with aggressive Therapies like Chemo- or Radiation- Therapy which are shortly described above. With increasing knowledge about the mechanisms of our Immune- System it became possible to use the bodies own immune system to fight cancer. PD-1 is a protein on T-cells that is responsible for the differentiation between healthy and cancerous cells. When PD-1 binds to the PD-L1 protein the T-cells are stopped from attacking the cell. Cancer cells have developed such PD-L1 proteins so they will not be recognized by the T-cells. With Checkpoint inhibitors like nivulomab it became possible to loose this blockade. When nivulomab binds to the PD-1, it can not longer attach to the PD-L1 on the cancer cells surface . Thus the T- cells can start an immune attack against the cancer. Another immune therapy that is already making its way to the clinic is the non- specific immune stimulation. Non-specific immune stimulation increase the immune response in vivo by stimulating the antigene presenting cells that recruite T-cells for tumor-attack. This is triggered by the injection of cytokines like interleukin-2 or interferon-α. Immune Therapies are already making their way to become a more and more effective therapy to fight cancer even if there are still many thing to impove. ^{[1] [2]}

Viral Gene Therapy

Gene therapy is a method to tackle cancer directly on a genetic level and can approach every genetic issue (cell growth self-sufficiency, insensitivity to anti-growth signals, evasion of apoptosis, sustained angiogenesis, limitless replicative potential and tissue invasion/ metastases) directly. Generally, there are three different approaches for gene therapy to fight cancer.

• Corrective strategy: Directly altering/reversing the mutated onco-/ tumor suppressor genes back to their original state.
• Cytoreductive strategy: Also called “Gene-directed enzyme Pro-Drug-Therapy”, which aims to directly kill cancer cells instead of restoring them to their original state, by introducing genes into the cells that code for lethal enzymes like nitroreductases.
• Immunomodulatory strategy: The therapy's goal is to restore the ability of the body's immune system to recognize and attack cancer/tumor cells by increasing the concentration of tumor-associated antigens or increase the expressing of the MHC-I.

Yet gene therapy has its limitations. The gene transfer conducted by viral vectors suffer from a poor eficiency, therefore making it difficult to complete the transfer in all cells. Also, the use of viral vectors can trigger the patient’s immune system, leading to the destruction of the viral vectors.^[3]

There are also several rather severe possible side effects, like…

• leukemia
• combined immunodeficiency diseases
• ornithine transcarbamylase deficiency (leading to death)

References

^[1]=Immunotherapy: Boosting the immune system to fight cancer
^[2]=http://www.nature.com/nature/journal/v537/n7620_supp/pdf/537S109a.pdf
^[3]=J. P. Hughes, G. Alusi, Y. Wang (The Journal of Laryngology & Otology, Volume 129, Issue 4, April 2015) Viral gene therapy for head and neck cancer