What is targeted therapy
Malignant tumors are composed of cells that typically have defects in genes involved in controlling their growth and survival, promoting uncontrolled cell multiplication. Genes responsible for organizing the tumor microenvironment also undergo changes, stimulating the spread of the disease. Targeted therapy represents a form of cancer treatment based on specific drugs directed at these defects.
In addition to being more effective, one of the most striking consequences of the specificity of targeted therapy is that, because it is aimed at targets that only tumor cells have, healthy cells are preserved. Preserving physiologically normal cells in the body minimizes the potential for undesirable side effects of treatment.
Targeted therapy is approved and already in use for the treatment of various types of cancer, and much research is underway to expand its benefits.
Mechanism of action of targeted therapies
Various types of cells make up the tissues and organs of the human body, such as those found in the brain, skin, or blood, each with a group of specific physiological functions defined by the genetic code. The genetic code determines the cellular production of proteins. Analogous to a production line, therefore, cellular functions are coordinated by the genetic code and effectively executed by proteins.
Cancer begins to develop when certain genes, previously healthy, undergo changes, a process called genetic mutation. Genetic mutations lead to abnormal production of proteins (both in quantity and function), allowing uncontrolled cell growth and consequently tumor development.
The process is quite complex and involves other conditions that facilitate and maintain each tissue/organ, which means that not every mutation is capable of developing cancer. To develop targeted therapies, genetic alterations that favor tumor development and ideally are not present in normal cells of the body are initially identified. Once one (or more) relevant mutations are identified, treatments that activate or neutralize the “defective” proteins encoded by these respective genes can be developed. Targeted therapy can also use these proteins to locate the abnormal cell and literally make it a target to “deliver” lethal substances.
Targeted therapies can target cancer cells in different ways, such as:
Targeted therapies can affect cancer cells in various ways, such as:
- Blocking signals that tell cells to grow and divide;
- Preventing cells from surviving longer than normal;
- Assisting the immune system in destroying cancer cells;
- Interrupting signals that help form blood vessels that nourish the tumor.
In summary, targeted therapy represents a significant technological advancement in which cellular targets are located and manipulated to block the tumor development process, redirecting cells to their physiological and non-proliferative route. It is a highly specific process and therefore more effective and with lower potential for toxicity compared to more conventional treatments such as chemotherapy, as it “spares” normal cells while “correcting” defective cells.
Types of targeted therapy
Targeted therapy involves various types of technologies and drugs with distinct purposes and mechanisms of action. Depending on the drug class, administration can be oral or intravenous. The two most commonly used types of targeted therapy are:
- Monoclonal antibodies – this type of drug, administered intravenously, locates and binds to a specific target on the outside of cancer cells or in the area around the tumor. They can be developed to carry harmful substances to cells (such as chemotherapeutics) and deliver them at the time of binding. They can act in conjunction with other treatments, enhancing the precision of chemotherapy and radiotherapy and increasing treatment effectiveness.orming new blood vessels) are an example of this type of targeted therapy: as tumors need blood vessels to receive nutrients, grow, and spread, angiogenesis inhibitors “starve the tumor” by preventing new blood vessels from forming around it. They are administered orally (capsules or tablets depending on the drug).
Currently, most targeted therapies are specific to each type of cancer, as the targets differ between tumor types. However, “agnostic therapies” are gaining importance. Agnostic targeted therapy is based on certain mutations that are independent of the organ of origin, focusing on the specific genetic alteration rather than the type of tissue in which the tumor process began.
How targeted therapy is chosen
Not all cases are candidates for targeted therapies; however, with the speed of research, more mutations are being identified, and new therapies are
Drugs of the “small molecule” class – because they are very small molecules, they can easily enter cells and target structures inside them. Angiogenesis inhibitors (which inhibit the process of fbeing developed, expanding the indications and access to these treatments. It is important that the indication be very precise for the treatment to be successful.
To properly choose the best targeted therapy for each patient, the doctor requests tests that analyze the specific molecular profile of the tumor, looking for therapeutic targets. From the identification of these characteristics, the most effective treatment is determined. For this, it is essential to conduct a thorough and meticulous analysis of the tumor material.
It is important to emphasize that this more assertive approach, based on precision medicine technology, has made treatment increasingly individualized, which increases the chances of good results. However, other treatment modalities (surgery, radiotherapy, chemotherapy) continue to have their indications and may be part of the therapeutic plan aiming at the best care for each patient.
Application of targeted therapies in practice
To make the understanding clearer, we have listed 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 receptor 2 (HER2), which stimulates the growth of tumor cells. When the cancer is HER2-positive, targeted therapy for breast cancer can be performed;
- Colorectal cancer – there may be an overexpression of the epidermal growth factor receptor (EGFR) protein. In this case, some targeted therapies can block EGFR and reduce or prevent 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 therapy for lung cancer that blocks EGFR can also reduce or prevent lung cancer growth. In addition, there are targeted drugs for lung cancers with mutations in the ALK, ROS, and BRAF genes;
- Chronic myeloid leukemia (CML) – most cases of CML occur due to 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 behave like cancer cells, and targeted therapies for leukemia can interrupt this process;
- Lymphoma – there is an exaggerated production 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 mutation in the BRAF gene, and there are some BRAF inhibitor targeted drugs with promising results in this scenario within melanoma targeted therapy. However, it is necessary to prove the presence of the mutation, as the use of these drugs can be harmful when it is not present.
Possible adverse effects and complications of targeted therapies
Despite having lower potential for toxicity, like any other treatment, targeted therapies present possible adverse effects characteristic of each class of medication. The main ones are:
- The most commonly observed adverse events with the use of targeted therapies are diarrhea and liver problems. There may also be difficulty in blood clotting and wound healing, hypertension, fatigue, mouth sores, nail changes, hair color changes, and other skin issues (such as skin rashes or dryness).
The good news, however, is that there are preventive and curative treatments for most of these side effects, which in most cases do not prevent the treatment from being carried out successfully.
Targeted therapy technologies are constantly and increasingly developing, progressively changing the landscape of cancer treatments. However, there are still inherent difficulties in the behavior of cancer that need to be overcome:
- Cancer cells can become resistant to targeted therapies, which inevitably occurs with all cells at some point in treatment. For this reason, in specific situations, they may work better when used in conjunction with other types of targeted therapies or cancer treatments, such as chemotherapy and/or radiotherapy;
- Some targets are quite complex due to the structure and function they play in the cell. For this reason, there is greater difficulty in developing targeted therapies directed at these targets, although ways to overcome these barriers are constantly being studied.
