Definition of Cancer

Cancer is a disease that occurs by the transformation of healthy cells into cancerous cells in our body. This disease can be classified as hereditary, also known as simply carried by genes, or sporadic (non-hereditary), which is caused by different types of factors that cause changes in the genes. Factors that cause cancer in sporadic cases include environmental factors, sunlight, carcinogenic substances, radiation, infection, diet, smoking-alcohol consumption, and stress. When considered on an organ or tissue basis, other factors such as endogenous (produced in the body) and exogenous (derived externally) hormones come into play depending on where the cancer occurs.

Cancer Formation at the Cellular Level

The transformation of a healthy cell into cancer is called carcinogenesis and it is known to be a very complex procedure when examined at the cellular level. While the transformation of a healthy cell into a cancer cell is generally observed through changes called mutations that occur in the cell DNA, it has become possible to detect these mutations and determine treatment protocols with developing technologies.

The resulting mutations can generally be classified as mutations that negatively affect cell growth, damage mechanisms, and repair mechanisms. These mutations are also observed in tumor suppressors and tumor-causing oncogenes*. In addition to the mutations that occur at the time of initial diagnosis of cancer, mutations that cause resistance may appear later upon treatment for the patient.

*Oncogene: These are protein-coding genes that have lost their control and play a role in the beginning of cancer development.

Treatment of cancer

Cancer treatment begins with imaging and pathological* diagnosis of cancer. During this diagnosis, imaging determines whether the cancer is regional or metastatic**, and microscopic examinations in pathology determine the character of the cells in the tissue taken from the patient, whether they have certain cancer markers, and specific molecular characterizations. During the diagnosis phase, the stage of the cancer is also reported.

Once the diagnosis is confirmed, the treatment protocol is determined according to where the primary area of the cancer is located. These protocols often include cancer surgery, chemotherapy and radiotherapy. Surgery may occur before or after therapy, depending on the location of the tumor. The aim of surgery is to remove all of the tumor, if possible, or as much of the tumor as possible, if not possible.

*Pathology: It is the branch of science that studies the causes, symptoms, and effects of a disease or disorder.

**Metastasis: It refers to the spread of cancer to a region farther from the organ where it originated.

Chemotherapy

Chemotherapy, described as a drug treatment for cancer, is routinely used depending on the organ/tissue and stage of the cancer. Chemotherapy aims to eliminate cancer cells by preventing their growth and damaging the cancer cells. Chemotherapy can consist of a single drug, but can also be applied as a combination of several drugs. These treatments can be administered orally or by injection into the vein and muscle.

Since cancer cells exhibit uncontrolled growth compared to normal healthy cells and also the defense mechanisms of cancer cells work stronger compared to healthy cells, drug treatments are highly toxic compounds to act on cancer cells. For this reason, side effects such as vomiting, hair loss, and skin reactions are usually unavoidable in patients as a result of chemotherapy treatments.

Chemotherapy treatments can be divided into neoadjuvant, adjuvant, and palliative treatments depending on the time and type of treatment. Neoadjuvant therapy is an approach that aims to shrink the tumor before surgery and is mostly used for cancers such as breast, colon, and rectal cancer. Adjuvant therapy is a type of chemotherapy that is administered after surgery. Palliative therapy, also known as supportive treatment, is a type of chemotherapy used to alleviate symptoms and improve quality of life.

Chemotherapeutic Drugs

Chemotherapeutic drugs, also known as antineoplastic drugs, are classified according to their mechanism of action and targets as alkylating agents, antimetabolites, antitumor antibiotics, mycosis inhibitors, hormones, nitrosoureas, plant alkaloids, and other anticancer drugs. Attempts are made to administer these drugs to patients at different times, taking into account their interactions with each other and their side effects.

Once the cancer is diagnosed and its stage determined, the choice of chemotherapeutic agent is primarily determined according to the NCCN (National Comprehensive Cancer Network) catalogs, which are recognized in many countries. Since the half-life of information in oncology is quite short, the information in this catalog is frequently updated and oncologists base their treatment decisions on these updates.

Radiotherapy

Radiotherapy is, as the name suggests, the treatment of cancer with high-energy radiation through the application of beams. These ionizing rays work by damaging the DNA of the tumor cells. Radiotherapy is used in the early or advanced treatment of almost all types of tumors. Radiation therapy that targets the tumor and its surroundings as much as possible also damages some healthy tissue nearby.

Radiotherapy can in turn be divided into adjuvant, neoadjuvant, primary, and palliative therapy. Adjuvant radiotherapy, which is used in particular for breast cancer, is defined as postoperative radiotherapy. Neoadjuvant radiotherapy aims to shrink the tumor before surgery. This radiotherapy, which is generally used for cancers such as lung and rectal cancer, ensures that fewer pieces of tissue are removed during surgery. Primary radiotherapy is radiotherapy used for non-surgical cancers such as vocal cord tumors. Palliative radiotherapy is a type of radiotherapy used to prevent the spread of cancer cells in advanced stages.

Recent Innovations in Cancer Treatment

As mentioned earlier, cancer treatments are determined on an organ/tissue basis depending on the stage of cancer, following important catalogs accepted in oncology. Although these treatment methods are successful, many cancer patients do not respond to the drugs, develop resistance* to the drugs later despite an initial response, and cancer recurrence is observed after treatment.

In recent years, many technological developments have shifted the definition of cancer treatment from the organ/tissue level to the individual level, adding the terms personalized cancer treatment and precision oncology to oncology. This advancement in cancer treatment has been achieved primarily through genomic projects and the ability to map patient-specific DNAs, RNAs, and proteins using advanced technologies. Simply put, RNA arises from DNA in the cell nucleus, and proteins arise from the RNA code.

Thanks to these genomic technologies, patient-specific mutations, RNA fusions, and, where applicable, protein differences can be identified and a treatment protocol developed for the patient. In this way, cancer treatment becomes personalized and more effective, and treatments that are applied to the patient without predicting their effectiveness can be prevented.

*Drug resistance: It is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition.

Approaches that target cancer tissue and its environment

Especially in solid tumors, tumor tissue is formed when cancer cells grow uncontrollably and begin to destroy tissue. Thanks to the advanced technologies mentioned above, structures specific to that cancer cell are discovered in the membrane of each cancer cell and also within the cell. By targeting the cancer cell directly, it is possible to both increase the effectiveness of the treatment and reduce the side effects. This type of treatment can be compared to packages that are sent directly to the right address by adding a stamp to the drug without visiting other addresses. Drugs packaged in this way can be called antigen-drug conjugates or antibodies directed at the tumor. Thanks to the structures attached to the drug, which we compare to a stamp, effective treatments can be observed in a short time.

In addition to these features discovered in cancer cells, the environment of cancer cells in tumor tissue, the so-called tumor microenvironment, amazes researchers daily. The immune cells in this environment, healthy cells from the same source, stem cells, fibroblast cells as well as the rich extracellular matrix are different in each patient and play a crucial role in many events such as cancer progression, drug reaching the tumor, and drug response. Immunotherapy, which was awarded the Nobel Prize in 2018, was introduced as a treatment approach in which lymphocytes*, one of the immune cells surrounding this cancer, are designed to recognize and eliminate cancer cells.

While all the studies that have been conducted in the field of cancer in recent years have contributed to the literature with crucial results, we are all very excited that precision oncology will have an important place in treatment in the near future and that much more effective treatments can be developed by assessing patient-specific cancer and its environment.

*Lymphocytes: A type of white blood cells that are part of the immune system. They help fight against foreign viruses, bacteria, and cancer in the body.

1. Massimo, A., et al. Distance as a Barrier to Cancer Diagnosis and Treatment: Review of the Literature. (2015). https://pubmed.ncbi.nlm.nih.gov/26512045/

2. Enrique, E., et al. Classification of anticancer drugs—a new system based on therapeutic targets. (2003). https://pubmed.ncbi.nlm.nih.gov/14585261/

3. Zitvogel, L., et al. Immune parameters affecting the efficacy of chemotherapeutic regimens. (2011). https://pubmed.ncbi.nlm.nih.gov/21364688/

4. Thariat, J., et al. Past, present, and future of radiotherapy for the benefit of patients. (2013). https://pubmed.ncbi.nlm.nih.gov/23183635/

5. Yılmaz, B.K., and Arga K.Y. Driving Precision Oncology to Clinical Practice: The Road Ahead from Biomarker Validation to Clinical Decision Systems. (2022). https://pubmed.ncbi.nlm.nih.gov/35549456/