Targeted Therapy

Targeted therapy works by utilizing medications that are made to look for characteristics particular to certain cancer cells or ones that affect their activity. Enzymes, proteins, or gene alterations may be among these traits and may be what's causing the disease to spread. Drugs used in targeted therapy are made to either directly attack cancer cells or to improve the efficacy of conventional cancer treatments like chemotherapy. Additionally, radiation therapy or surgery may be utilized in conjunction with the medications.

A type of precision cancer treatment, targeted therapy is a type of chemotherapy (drug therapy). Targeted therapy directs medications to particular characteristics of cancer cells, in contrast to traditional or standard chemotherapy, which targets rapidly proliferating cells throughout the body, whether they are cancerous or not. The goal of conventional chemotherapy is to eradicate cancer cells that the body has already produced. Targeted therapies aim to obstruct or stop cancer cells from replicating and limit the growth of new cancer cells. Targeted therapies are less likely to destroy normal cells than conventional chemotherapies because of how they operate differently.

To establish whether a patient might benefit from a targeted therapy that is now accessible, oncologists rely on cutting-edge genomic testing and other laboratory tests or diagnostic techniques. The treatments are tailored to the particular tumors they target or to particular characteristics of cancer cells, wherever they manifest themselves in the body.

Drugs used in targeted therapy interfere with particular chemicals present in proteins or receptors on and in cancer cells. Targeted therapy aims to inhibit or reduce the growth of tumors by attacking or interfering with the genetic characteristics of the cells that control cell growth and division. Targeted therapy depends on the medications it employs or carries to do the assaulting, in contrast to immunotherapy, which encourages a person's immune system to detect cancer cells as alien bodies and fight them.

How does targeted therapy work?

Cancer develops when the DNA in a cell mutates or becomes defective. Targeted therapy drugs are designed to bypass normal cells and zero in on specific targets—some are mutations on the surface of cancer cells, others are inside the cell. Once they reach their target, these drugs may:

  • Shut down signals that allow cancer cells to grow
  • Prevent cancer cells from making new blood vessels, which feed tumors
  • Stop production of hormones that may help tumors grow
  • Repair the ability of cells to shut down if they are defective
  • Carry radiation or chemotherapy drugs directly to the mutated cell

For example, trastuzumab (Herceptin®)—a drug designed to shut down cancer cell growth signals—is used in the treatment of some breast cancers. It targets defective human epidermal growth factor receptor 2 (HER2) proteins. HER2 is a protein found on the surface of normal cells that sends signals that help cells grow. But it runs amok in about 25 percent of breast cancer patients and ends up producing too many receptors, causing cancer cells to grow wildly.

Another example, Bevacizumab (Avastin®), is a drug that may disrupt a cancer’s ability to make new blood vessels, which would increase the blood supply it needs to feed itself. All cells produce vascular endothelial growth factor (VEGF), a protein that helps cells form new blood vessels through a process called angiogenesis. Drugs such as bevacizumab, an angiogenesis inhibitor, are designed to block VEGF and stop a tumor from forming new food supplies.

How are the targets found?

Before determining whether to use a targeted cancer therapy, oncologists need to know where they are aiming. To assist in this form of precision medicine, certain tests may help determine which DNA mutation is driving the cancer’s behavior. These tests include:

Advanced genomic testing: In this analysis, the genetic profile of a tumor is scanned for specific mutations that may propel the tumor’s growth, progression or other behaviors. If a known mutation is found, it may be matched to a specific drug therapy targeting that mutation.

Pathology tests: These include examination of tissue samples, blood samples or stool samples. By searching for mutant proteins or an overabundance of protein in cancer cells, pathologists may identify potential targets for therapy. They may also look for abnormalities in chromosomes inside cancer cells.

Genetic testing: These tests may determine whether a patient has a hereditary gene mutation linked to his or her cancer.

What types of cancer drugs are used in targeted therapy?

There are different types of targeted therapy, depending on the specific cancer features detected. Below are some of the potential treatment options.

Monoclonal antibodies, also known as therapeutic antibodies, are immune system proteins produced in a laboratory. These engineered molecules are designed to attach to specific targets found on cancer cells. They may directly stop cancer cell growth or cause the cancer cells to self-destruct. They may also be used to carry toxins such as chemotherapeutic agents or radioactive substances to tumor cells to cause cell death. In immunotherapy, monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system.

Small-molecule drugs are better able to access cells and locate their prime target due to their low molecular weight and size. Some examples of small-molecule drugs include epidermal growth factor receptor (EGFR) inhibitors, angiogenesis inhibitors and apoptosis inducers.

Epidermal growth factor receptor (EGFR) is a protein, found on the surface of some normal cells, that contributes to cell growth. When cancer cells have a large number of these receptors, they’re able to grow and divide rapidly. EGFR inhibitors are used in targeted therapy to block these proteins and prevent cancer from growing.

Angiogenesis inhibitors are another drug used in targeted therapy. Angiogenesis—the formation of new blood vessels—is controlled by chemical signaling. In healthy people, these chemical signals only appear when needed: during growth and healing. However, the signals may get crossed and allow blood vessels to grow abnormally. Tumors need a supply of blood to grow, and without it, they can’t grow or spread. The idea behind angiogenesis inhibitors is to prevent or block the supply of blood vessels that feed tumors in order to starve them to death. Angiogenesis inhibitors don’t block the growth of tumors, but rather the tumors’ blood supply. Angiogenesis inhibitors are typically given over a long period of time, in combination with other therapies.

To function normally, the body needs to shed unneeded and abnormal cells. It does so in a complex process of controlled cell death called apoptosis. Cancer cells are able to avoid apoptosis. Apoptosis inducers are used to allow apoptosis, helping to prevent recurrence and metastasis.

Hormone therapies target specific hormones, such as estrogen, to decrease the amount of that hormone in the body, slow the production of the hormones or block them entirely from feeding cancer cells.

What are side effects of targeted therapy?

Because the treatments are designed to target cancer cells and spare damage to healthy cells, targeted therapy drugs may cause fewer side effects than conventional treatments such as chemotherapy. However, depending on the type of targeted therapy used, the treatment may also alter cell function, potentially leading to side effects that should be monitored and managed.

Targeted therapy side effects may include:

  • Rashes or dry or flaking skin
  • Cracked or inflamed fingernails or cuticles
  • Diarrhea or digestive problems
  • Impaired blood clotting or wound healing
  • High blood pressure
  • Fatigue

Targeted therapy drugs are powerful and may cause side effects in caregivers and family members who come in contact with them. If you’re taking a targeted therapy at home, be aware of special handling, storage and disposal requirements.

What types of cancer do targeted therapies treat?

The U.S. Food and Drug Administration (FDA) has approved targeted therapy drugs for many cancers, including the most common types, such as:

  • Breast cancer
  • Bladder cancer
  • Colorectal cancer
  • Kidney cancer
  • Leukemia
  • Liver cancer
  • Lung cancer
  • Lymphoma
  • Prostate cancer

The FDA has also approved targeted therapy drugs to treat solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion. In these tumors, the NTRK gene has broken off one chromosome and fused with another, which may promote tumor growth. This is a tumor-agonistic therapy diagnosed based on specific genetic features of the cancer, regardless of where in the body it originated.

How are targeted therapy drugs delivered?

How and where targeted drugs may be given to cancer patients depend on many factors, including clinical considerations and personal preferences. They may be administered:

  • Orally: In pill, capsule or liquid form, taken by mouth, usually at home
  • By injection: Delivered through a needle into a vein, muscle or under the skin
  • By infusion: Delivered into a vein through an intravenous drip, a process that may take several hours

Small-molecule drugs are usually given in pill or capsule form. Monoclonal antibodies are usually given by injection or infusion. Patients whose treatment plan includes more frequent injections or infusions may choose a port or catheter to deliver their drug more efficiently and with less pain.