Cancer Development and Different Treatment Approaches

1. Cancer Development

2. Properties and Metabolism of Cancer Cells

3. Cancer Treatment Approaches
3.1. Radiotherapy
3.2. TrueBeam X
3.3. Trilogy
3.4. Elekta Versa
3.5. Linac
3.6. Chemotherapy
3.7. Surgery
3.8. Hormone Therapy
3.9. Immunotherapy
3.10. Gene Therapy

REFERENCES

Internet References

1. Cancer Development

Cancer is the uncontrolled division, proliferation, and accumulation of cells in an organism. It can affect a single organ as well as spread to distant organs and show its effect. Cancer has been a common problem in humans and animals throughout known history (Pavlopoulou A. et al., 2015). Cancer is a complex disease that occurs with uncontrolled division and proliferation of cells and under the influence of genetic and environmental conditions. Cancer is also a personal disease, although there are more than 100 known types of cancer and standard approaches have been developed for certain types of cancers (Fitzmaurice C. et al., 2015). It is not surprising that people have different responses to similar treatments since the DNA of any person in the world is not alike. With the advancement of technology, new treatment methods are being developed in addition to the treatments available today. In addition to the standard chemotherapy, radiotherapy and surgical methods, vaccines, biological, hormonal, targeted and gene therapies are increasingly being used. Although some standards have been determined, different approaches and treatments are applied for each type of cancer (Guo C., et al., 2013).

The genes on the chromosomes are tightly packed, and physical or chemical changes on these genes can directly affect the cell's function. Although DNA repair systems try to restore the function of the gene due to damage to the gene, success is not always achieved. In this case, inadequate or incorrect production of proteins, which are the products of genes, disrupts cellular functions. Another factor that changes the function of the gene is epigenetic modifications such as methylation, acetylation, phosphorylation, ribosylation, which change the function of the gene without changing its structure. These modifications can only act on a specific site, or they may appear as regional deletions, insertions, or inversions that affect all or a large part of the chromosomes. Three gene groups are responsible for the formation of cancer. These are oncogenes, tumor suppressor genes, and DNA repair genes. Proto-oncogenes, which are normal genes that enable cell growth and differentiation, can become active and turn into oncogenes due to mutations, increased gene expression, gene duplications, and/or chromosomal rearrangements. Examples of the most known oncogenes are genes such as RAS, Erk, MYC. The gene groups that control the division and proliferation of the cell, initiate DNA repair in case of damage, and trigger apoptosis if the repair attempt fails, are called tumor suppressor genes. The most known and most studied of these is the TP53 gene. Deletions, point mutations, epigenetic silences, improper separation of chromosomes, and mitotic recombinations can lead to loss of function of the tumor suppressor gene, leading to loss of control in the cell cycle and carcinogenesis.

Cancer-causing agents are called carcinogens. These are examined in 3 groups: physical, chemical, and biological. Radiation, cigarette smoke, and viruses are examples of these carcinogens, respectively (Table 1) (Blackadar CB., 2016).

Table 1. Carcinogens and Cancer Types. When we look at the rates of development of cancer types, the most common type of cancer that causes death in both men and women is lung cancer. In the second place, prostate cancer in men and breast cancer in women (Siegel RL. et al., 2016).

Abbildung in dieser Leseprobe nicht enthalten

Cancer is responsible for 1 in 6 deaths globally. Tobacco using has approximately 22% rate which is the highest percentage of cancer deaths (https://www.who.int/news-room/fact-sheets/detail/cancer). The most common cancer types are lung and breast cancers worldwide. Respectively 2,093,876 and 2,088,849 cases were diagnosed in these cancer types in 2018. According to 2018 data, the most common cancer type among women is breast cancer and the most common cancer type among men is lung cancer (https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data) Common types of cancer types in both genders and separate genders are shown in Table 2 and Table 3.

2. Properties and Metabolism of Cancer Cells

Cancer cells are clever cells. They have their metabolism. Under normal conditions, when cells receive signals from the outer membrane, they grow and divide and multiply. The signals coming from outside enter into the cell, transferred to the nucleus and the process begins. Before the cell divides, it checks its surroundings and checks whether there are enough nutrients, whether there is room to grow, and begins to grow if conditions are favorable. They grow until they reach the predetermined height and number and stop growing as they touch each other. This is called contact inhibition (stop contact growth).

Table 2. Incidence of cancer types globally for both sexes in 2018 (https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data)

Abbildung in dieser Leseprobe nicht enthalten

Table 3: Top three cancer types and their number of cases in men and women according to 2018 data (https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data)

Abbildung in dieser Leseprobe nicht enthalten

If the DNA or one of the elements of the cell is damaged, the cells stop growing and dividing and pass to a phase called the G0 phase to be repaired. If the cell is repaired with the necessary arrangements here, it enters the circulation again and continues its life. However, if it is damaged beyond repair, it is sent to death programmatically through the mechanism called apoptosis, or the immune system cells destroy the damaged cell by eating it. Thus, transferring the damaged DNA to the next generations is prevented. Cancer cells have many features that normal cells do not have.

Receivers (receptors) on the cell surface receive signals more often

- It has its own signal systems that enable uncontrolled reproduction.
- It does not stop the division after contact with the next cell and continues to grow and multiply
- While healthy cells can use any type of food, cancer cells can only use glucose from glycolysis. They absorb sugar approximately 100 times more than normal cells and produce energy by producing lactate (Warburg effect).
- They can create new vascular systems by affecting the stroma around them to get the necessary nutrients and oxygen (neo-vascularization)
- Replicate and reproduce infinitely by fixing their telomeres or maintaining telomerase activity.
- They can enter the circulatory system and move to a distant place and start cancer in a new setting (metastasis)
- They can avoid apoptosis
- They are not genetically and epigenetically stable

Cancer cells are clever cells because they hold on to life with little oxygen, little food, resistance to harsh conditions, and turning these conditions in their favor over time. Cancer cells can be transformed over time, that is, deformed. While normal cells can grow and survive by clinging to a certain surface, cancer cells can live and grow and reproduce without holding anywhere. An abnormal cell occurs with the action of carcinogens from the normal cell. This cell divides to form a tumor mass. The resulting tumor mass needs food for its energy needs. They provide this nutrient requirement from glucose in our body. They form blood vessels branching out of our veins. This process is called angiogenesis. With these vascular networks, they use glucose in our blood as a source of energy to increase their reproduction. A cell that then leaves this tumor mass can pass to a different organ using the blood or lymph tract. We call this transfer metastasis. If these cancerous cells begin to spread to different regions in the organ where they first appeared, we call it an invasion (Figure 1).

Many types of cancer do not show symptoms at the beginning and it should be remembered that not all cancer types are the same. General symptoms, depending on the type of cancer, may vary. Therefore, the approach to each type of cancer is different. However, with early diagnosis, good care increases expected life expectancy and quality. Therefore, new methods are being tried. Although regular checks are important in the early diagnosis of cancer, many people have their checks after serious health problems. People with a family history of cancer should be more sensitive about routine checks. X-ray, blood tests, computed tomography scans, magnetic resonance imaging (MRI), endoscopy, and genetic imaging tests are tools that can be used in early diagnosis of cancer.

3. Cancer Treatment Approaches

Treatment approaches used in cancer treatment are radiotherapy, chemotherapy, and surgical methods. However, these methods, known as the gold standard, have advantages and disadvantages. Therefore, in addition to these conventional methods, various immunological and biological treatment methods are developed.

Abbildung in dieser Leseprobe nicht enthalten

Figure 1. Cancer Pathway (Inspired by Kim et. al., 2009)

It is possible to make an early diagnosis with genetic tests to determine cancer susceptibility in individuals with a family history of cancer. In addition, the reasons behind the disease can be determined more precisely with these tests. Although useful information can be obtained thanks to these tests, it is possible that the person will never get the disease even though he has the gene that causes the disease.

3.1. Radiotherapy

Radiotherapy (RT) is a treatment method based on killing cancerous cells using ionizing rays. While it can be done by targeting only a certain part of the body, treatments targeting the whole body are also applied. The aim of radiotherapy is to provide protection of healthy tissues and risky organs while it gives the maximum dose to the tumor. RT is divided into two as external RT and brachytherapy, depending on how the radiation is applied to the patient. In external RT, radiation is applied to the patient at a certain distance with appropriate devices. Brachytherapy is the application of radiation by placing the radioactive source in or around the tumor. Devices used in RT also vary depending on these applications (Kinhikar RA. et al., 2014).

Different radiotherapy devices can be used in the treatment of radiotherapy depending on the general health of the patient, the type and stage of cancer (Varela G et al.,2016).

- The choice of the radiation source to be used is determined by the type of tumor, its location in the body, and especially its depth.

TrueBeam, Trilogy, Elekta Versa HD, and Linac devices are used during radiotherapy treatment.

Table 4. Examples of frequent tests depending on cancer types

Abbildung in dieser Leseprobe nicht enthalten

3.2. TrueBeam X

TrueBeam system, which is a new generation beam technology, is used in radiation oncology for irradiation of the tumor in every part of the body.

- TrueBeam has advantages such as robotic imaging, automatic patient positioning, motion management and dynamically synchronizing therapy. In addition, TrueBeam is often used for the treatment of tumors in hard-to-reach areas.

The biggest difference from other radiotherapy devices is the ability to increase the high dose rate. Thus, radiotherapy significantly reduces the session, duration, and number.

3.3. Trilogy

- Combining the features of all radiotherapy devices, Trilogy ensures that the correct intervention is performed in a shorter time and in the most appropriate amount.
- The uses of each of the methods used in the Trilogy are different; varies according to the structure of the tumor and the patient.
- Trilogy device can be examined in 3 different methods as IMRT, IGRT, SRT / SRC:

1. In the IMRT (Intensity Adjusted RT) method, the intensity of the radiation in the cancerous region is adjusted and the desired dose distribution is closest to the ideal. While high doses can be applied to the tumor, healthy tissues are also protected to the maximum.
2. In the IGRT (Imaging Guided RT) method, the patient can be visualized not only before the treatment but also during the treatment and the shifts in the area to be irradiated can be prevented. In the IGRT method, the accuracy of the treatment area of ​​the patients is certain with the imaging added to the device.
3. With the SRT / SRC method, spot irradiation can be performed on very small tumors of a millimeter level. With this irradiation performed as a point shot, a high dose of radiation is given to the tumor and healthy tissues are preserved (Chen H. et al., 2015).

[...]