What is targeted therapy?
Targeted therapy is a type of cancer treatment that uses drugs designed to “target” cancer cells without affecting normal cells.
Cancer cells typically have changes in their genes that make them different from normal cells. Genes are part of a cell’s DNA that tell the cell to do certain things. When a cell has certain gene changes, it does not behave like a normal cell. For example, gene changes in cancer cells might allow the cell to grow and divide very quickly. These types of changes are what make it a cancer cell.
But there are many different types of cancer, and not all cancer cells are the same. For example, colon cancer and breast cancer cells have different gene changes that help them grow and/or spread. Even among different people with the same general type of cancer (such as colon cancer), the cancer cells can have different gene changes, making one person’s specific type of colon cancer different from another person’s.
Researchers have also learned that the environment in which different cancers start, grow, and thrive are not always the same. For example, some cancers have certain types of proteins or enzymes send certain messages to tell the cancer cell to grow and copy itself.
Knowing these details has led to the development of drugs that can “target” these proteins or enzymes and block the messages being sent. Targeted drugs can block or turn off signals that make cancer cells grow, or can signal the cancer cells to destroy themselves.
Targeted therapy is an important type of cancer treatment, and researchers will develop more targeted drugs as they learn more about specific changes in cancer cells. But so far, only a few type of cancers are routinely treated using only these drugs. Most people getting targeted therapy also need surgery, chemotherapy, radiation therapy, or hormone therapy.
How is it different from chemotherapy?
Targeted therapy drugs, like other drugs used to treat cancer, are technically considered chemotherapy. But targeted therapy drugs don’t work the same way as traditional or standard chemotherapy (chemo) drugs. Targeted drugs zero in on some of the changes that make cancer cells different from normal cells. This makes them work differently from chemotherapy in two key ways:
- Because of their targeted action, these drugs have an effect on the cancer cells and mostly leave normal, healthy cells alone. Traditional chemotherapy is cytotoxic to most cells, meaning it can damage normal, healthy cells in addition to damaging and killing cancer cells.
- Targeted drugs often work by blocking cancer cells from copying themselves. This means they can help stop a cancer cell from dividing and making new cancer cells. Traditional chemotherapy, however, kills cancer cells that have already been made.
How targeted therapy works
Targeted therapies are made to find and attack specific areas or substances in cancer cells, or can detect and block certain kinds of messages sent inside a cancer cell that tell it to grow. Some of the substances in cancer cells that become the “targets” of targeted therapies are:
- Too much of a certain protein on a cancer cell
- A protein on a cancer cell that is not on normal cells
- A protein that is mutated (changed) in some way on a cancer cell
- Gene (DNA) changes that are not in a normal cell.
The action of targeted drugs can work to:
- Block or turn off chemical signals that tell the cancer cell to grow and divide
- Change proteins within the cancer cells so the cells die
- Stop making new blood vessels to feed the cancer cells
- Trigger your immune system to kill the cancer cells
- Carry toxins to the cancer cells to kill them, but not normal cells
The action of the drugs can affect where these drugs work and what side effects they cause.
Targeted therapy as precision medicine
Targeted therapy is sometimes called precision medicine or personalized medicine. This is because they are made to exactly target specific changes or substances in cancer cells, and these targets can be different even when people have the same type of cancer. Certain types of tumors are tested for different targets after a biopsy or surgery, and this can help find the most effective treatment. Finding a specific target makes matching patients with treatment more precise or personalized.
Some targeted drugs are more “targeted” than others are. Targeted therapies are classified as either small or large molecule drugs.
- Small molecule drugs are tiny enough to enter a cancer cell once they find it. They work by targeting a specific substance inside the cell and blocking it.
- Large molecule drugs usually cannot fit into a cell. They work by attacking then weakening or destroying proteins or enzymes on the surface of the cell. They are often described as a “lock and key” because the molecule is like a key that opens the enzyme or protein on the surface of the cell like a lock. The key fits into the lock, allowing the drug to work.
Many kinds of cancer can be treated with targeted therapies, and there are many different types of targeted therapies. Here are some types with a few examples of how they are used.
- Angiogenesis inhibitors: These block the formation of new blood vessels that feed and nourish the cancer cells. Example: bevacizumab (many different cancers).
- Monoclonal antibodies: These might deliver molecules by themselves or molecules with drugs into or onto the cancer cell to kill it. Examples: alemtuzumab (certain chronic leukemias), trastuzumab (certain breast cancers), cetuximab (certain colorectal, lung, head and neck cancers). NOTE: Some monoclonal antibodies are referred to as targeted therapy because they have a specific target on a cancer cell that they aim to find, attach to, and attack. But other monoclonal antibodies act like immunotherapy because they make the immune system respond better to allow the body to find and attack cancer cells more effectively.
- Proteasome inhibitors: These disrupt normal cell functions so the cancer cells die. Example: bortezomib (multiple myeloma)
- Signal transduction inhibitors: These disrupt cell signals so that they change the actions of the cancer cell. Example: imatinib (certain chronic leukemias)
What are the side effects of targeted cancer therapies?
Scientists had expected that targeted cancer therapies would be less toxic than traditional chemotherapy drugs because cancer cells are more dependent on the targets than are normal cells. However, targeted cancer therapies can have substantial side effects.
The most common side effects seen with targeted therapies are diarrhea and liver problems, such as hepatitis and elevated liver enzymes. Other side effects seen with targeted therapies include:
- Skin problems (acneiform rash, dry skin, nail changes, hair depigmentation)
- Problems with blood clottingand wound healing
- High blood pressure
- Gastrointestinal perforation (a rare side effect of some targeted therapies)
Certain side effects of some targeted therapies have been linked to better patient outcomes. For example, patients who develop acneiform rash (skin eruptions that resemble acne) while being treated with the signal transduction inhibitors erlotinib (Tarceva®) or gefitinib (Iressa®), both of which target the epidermal growth factor receptor, have tended to respond better to these drugs than patients who do not develop the rash. Similarly, patients who develop high blood pressure while being treated with the angiogenesis inhibitor bevacizumab generally have had better outcomes.
The few targeted therapies that are approved for use in children can have different side effects in children than in adults, including immunosuppression and impaired sperm production.
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