Targeted therapy is an oncological treatment made with drugs whose objective is to target one or more specific points in the body, such as genes and proteins involved in the growth and survival of cancer cells in a particular tumor, the environment in which the tissue is located. that helps the cancer to grow and survive or just the tumor cells. At the same time, healthy cells are spared and preserved.
It is approved for use in different types of cancer, and much research is underway to further expand the neoplasms that may benefit from it.
Mechanism of action of targeted therapies
Different types of cells form the tissues of the human organism, such as those present in the brain, skin or blood, and each one of them has a specific function. Cancer begins to develop when certain genes in these previously healthy cells change and become abnormal. This process is called genetic mutation.
Genes tell cells how to make the proteins that keep them working properly. If these genes mutate, so do these proteins. As a result, cells begin to divide exaggeratedly or very quickly, allowing them to live much longer than they normally would. This leads to uncontrolled cell growth, forming a tumor.
To develop targeted therapies, genetic alterations that help the tumor to grow and change are initially identified. A potential target for this therapy would be a protein that is present only in cancer cells. Once the mutation is found, targeted therapies can be developed. These are individualized and specific treatments, which can be taken orally or intravenously.
Targeted therapies can target cancer cells in different ways, such as:
- Blocking or turning off signals that tell cancer cells to grow and divide;
- Preventing cells from surviving longer than normal;
- Assisting the immune system in the destruction of cancer cells;
- Interrupting the signals that help blood vessels form; and
- Depositing toxic and lethal substances inside cancer cells.
Types of targeted therapy
There are several types of targeted therapy. The most commonly used are:
- Monoclonal antibodies – this type of drug blocks a specific target on the outside of cancer cells or in the area around the cancer/tumor. Monoclonal antibodies are able to send toxic substances directly into cancer cells – for example, they can help chemotherapy and radiation therapy target these cells more precisely. It is administered intravenously; and
- Small molecule drugs – work by blocking the process that helps cancer cells multiply and spread. Because they are very small molecules, they are able to easily enter cells and reach targets inside them. Inhibitors of angiogenesis (the process of making new blood vessels) are examples of this type of targeted therapy: as the tumor needs blood vessels to receive nutrients, grow and spread, angiogenesis inhibitors cause the tumor to “die of death”. hunger” by preventing new blood vessels from forming around you. Its use is orally (capsules or tablets).
Other types of targeted therapies are immunotherapies, different types of angiogenesis inhibitors, and apoptosis inducers (therapies that induce cell death, or apoptosis).
Some targeted therapies are specific to a type of cancer, while so-called tumor-agnostic or site-agnostic treatment can treat the disease in any region of the body, as they focus on the specific genetic change rather than the type of cell present.
How the target therapy is chosen
To choose the best targeted therapy for each patient, the doctor requests tests that analyze specific factors of the tumor, such as its genes and proteins, among others. From the identification of these characteristics, the most effective treatment is determined.
Application of target therapies in practice
For clarity, we list some types of cancers that benefit from currently available targeted therapies:
- Breast cancer – 20% to 25% of breast cancers have an excessive amount of a protein called human epidermal growth factor 2 (HER2) receptor, which stimulates the growth of tumor cells. When the cancer is HER2 positive, it can be treated with targeted therapies;
- Colorectal cancer – Epidermal growth factor receptor (EGFR) protein may be overexpressed. In this case, some targeted therapies can block EGFR and reduce or stop tumor growth. Another option in colorectal cancer is to use a drug that blocks vascular endothelial growth factor (VEGF), as this protein helps in the formation of new blood vessels (which nourish the tumor);
- Lung cancer – Targeted therapies that block EGFR can also reduce or stop the growth of lung cancer. In addition, there are drugs that target lung cancers with mutations in the ALK, ROS and BRAF genes;
- Chronic myeloid leukemia (CML) – most cases of CML occur through the formation of a gene called BCR-ABL, which leads to the production of a protein with the same name. As a result, normal myeloid cells begin to behave like cancer cells, and targeted therapies are able to stop this process;
- Lymphoma – there is an overproduction of B cells, a type of white blood cell that fights infections. In this case, targeted therapies block the enzyme that leads to this production; and
- Melanoma – about half of melanomas have a BRAF gene mutation, and there are some BRAF inhibitor target drugs with promising results in this scenario. However, it is necessary to prove the presence of the mutation, since the use of these drugs can be harmful when it is not present.
Possible adverse effects and complications of targeted therapies
Just like any other treatment, targeted therapies have possible adverse effects. The main ones are:
- Cancer cells can become resistant to targeted therapies. For this reason, in specific situations they may work better when used together with other types of targeted therapies or cancer treatments, such as chemotherapy and/or radiotherapy;
- Some targets are quite complex due to their structure and the role they play in the cell. For this reason, there is greater difficulty in the development of targeted therapies aimed at them, although ways to overcome these barriers are constantly being studied;
- The most commonly observed adverse events with the use of targeted therapies are diarrhea and liver problems. There may also be difficulty with blood clotting and wound healing, hypertension, fatigue, mouth sores, nail changes, hair color change, and other skin conditions (such as skin rashes or xerosis/dryness).
The good news is that there are preventative and curative treatments for most of these side effects.
