Targeted cancer therapy is a new-generation cancer treatment method that uses drugs designed to "target" cancer cells. These drugs let treat cancer with a minimal effect on normal cells. As a result, side effects experienced by the patients are significantly reduced. So let's take a closer look at this treatment method.
Targeted therapy is a new-generation cancer treatment method that uses drugs to attack the specific parts of cancer cells to stop their growth, division, and spreading.
Targeted cancer therapy drugs attack mutated proteins located inside or on cancer cells.
Targeted cancer therapy medicines are classified into two main groups – small-molecule drugs and monoclonal antibodies.
Targeted therapy is a fairly effective cancer treatment method. However, breakthroughs in science may help to create even more effective drugs.
The development of targeted cancer therapy
Until the late 1990s, the mainstay of cancer treatment has been chemotherapy drugs. These drugs work systemically by killing all actively dividing cells in the organism causing severe side effects as well as the formation of even more aggressive forms of cancer. Latter shortcomings have encouraged the search for new, more effective, and cancer cell-specific treatment methods. This finally led to the development of targeted cancer therapy directed to specific parts of cancer cells (proteins, genes, etc.) called “targets”, that help cancer to divide, grow and spread.
How targets of targeted therapy drugs are selected and identified?
All types of cells in the body contain thousands of proteins. Their interaction with each other creates a complex intracellular communication system (called “signaling pathways”) that controls cell growth, division, or even death. Latter proteins form when a specific enzyme inside the cell scans specific DNA sequence sites – called genes. During the such scan, the genes serve as information that specifies the order in which different amino acids must be connected to finally form the protein encoded by the gene (Figure 2).
Depending on the type of cancer, its cells could have different mutations in their genes. Therefore, when specific enzymes read the information from the mutated genes, mutated proteins can form (Figure 1). These mutated proteins in turn disrupt the smooth functioning of the intracellular communication system. And in the case of cancer cells, this leads to the formation of distorted signals that start to encourage the cell to grow and multiply out of control. Exactly these mutated genes and proteins are the “targets” of targeted cancer therapies drugs.
However, it is important to mention, that usually cells from different types of cancer, or even the same type but of different patients, are not the same. For example, prostate and colon cancer cells can have different gene mutations that facilitate their growth and spreading. Respectively, if two different patients have the same type of cancer, the gene changes in these cancers’ cells can vary. Accordingly, to develop new targeted drugs which could be adapted the most optimally, the researchers try to identify mutations that are the most common between different cancer types as well as between different patients’ cancer cells.
Types of targeted cancer therapy
Due to such a wide variety of possible “targets”, many different types of targeted cancer therapy drugs are developed and used in clinics. Based on how they work they are classified into different groups. Two main types of drugs can be distinguished - small-molecule drugs and monoclonal antibodies.
Small-molecule drugs: these drugs are extremely small, so they are capable of getting inside the cell where they do their job by attacking (inhibiting/blocking) various intracellular proteins. Depending on their targeted protein, drugs can be divided into different groups. The table below shows the main groups of small-molecule drugs.
The main types of small-molecule drugs
|Type||Mechanism of action|
|Tyrosine kinase inhibitors (TKI)||Inhibits the proteins called tyrosine kinases from sending signals that tell cancer cells to divide, grow, and spread.|
|Mammalian target of rapamycin (mTOR) inhibitors||Block the protein called mammalian target of rapamycin, thus preventing it from sending signals to cancer cells to grow and spread.|
|Poly (ADP-ribose) polymerase (PARP) inhibitors||Inhibit the protein called poly (ADP-ribose) polymerase, which repairs damaged DNA in cancer cells. Cells containing damaged DNA cannot further survive, thus the cancer is stopped from multiplying.|
|Cyclin-dependent kinase (CDK) inhibitors||Block the protein called cyclin-dependent kinase from sending signals that tell cancer cells to divide and spread.|
Monoclonal antibodies: these drugs are synthetic (lab-made) versions of natural immune system proteins called antibodies. The human body makes them help organism fight infections.
Monoclonal antibodies are much bigger than small-molecule drugs, so they cannot pass inside the cell. Instead, they are designed to act on targets located on the cell surface or right around them (also known as “targets in the extracellular environment”). Different types of monoclonal antibodies are manufactured to treat cancer. They can be classified as targeted therapy or immunotherapy drugs.
Targeted therapy antibodies have a specific target on a cancer cell to which they attach and inhibit its action. Whereas immunotherapy drugs do not inhibit their targets, but instead activate the patient's immune system to respond better and in this way allow the body to find and attack cancer cells more effectively.
The main types of monoclonal antibodies used in cancer treatment are described in the table below.
Main types of monoclonal antibodies
|Type||Mechanism of action|
|Angiogenesis inhibitors||Block various proteins involved in the formation and growth of new blood vessels. This reduces the blood supply to a tumor and slows or stops its growth.|
|Human epidermal growth factor receptor 2 (HER2) -targeted agents||Inhibit the protein called human epidermal growth factor receptor 2 (or even kill the HER2-positive cells). Elevated levels of this protein in cancer cells cause them to grow and multiply uncontrollably.|
|anti-CD20 monoclonal antibodies||Attach to a protein called CD20 to help the patient organism recognize cancer cells. This protein in higher-than-normal amounts is detected in patients with certain types of B-cell lymphomas and leukemia.|
How to know which kind of targeted therapy drugs are prescribed for you?
By the generic name of the drug, the patient can easily understand whether he or she is prescribed small-molecule drugs or monoclonal antibodies. The small-molecule drugs' generic names end in “-ib”. For example, erlotinib is a medication used to treat non-small cell lung cancer and pancreatic cancer. While the generic names of monoclonal antibodies end with the suffix "-mab." For example, trastuzumab is a monoclonal antibody used to treat breast cancer and stomach cancer.
The future of targeted therapy
Recent progress in molecular cancer biology has allowed scientists to find out novel possible “targets” for new medicines. Moreover, along with new small-molecule or monoclonal antibody drugs, researchers seek to develop new types of targeted therapy drugs (e.g., antisense oligodeoxynucleotides, small interfering RNA (siRNA), etc.). It is aimed that the “targets” of these drugs would be cancer cell genes thus enabling these new medications to act with even more increased accuracy.
Therefore, we can have reasonable expectations that soon science will make cancer diagnosis seem not so scary to the patient.