Watch the Cancer.Net Video: What is Targeted Therapy? with Nicholas Vogelzang, MD, adapted from this content.

Until recently, cancer treatment was largely based on the location in the body where the tumor began, such as the lung or breast. Now, cancer treatment increasingly depends on specific factors of a person's tumor, such as gene mutations (changes) or proteins that are often characteristic of cancer cells, regardless of the original location of the cancer. Targeted therapy is a treatment that targets a cancer's specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Unlike previous generations of cancer chemotherapies that were developed to interfere with cancer cells as they divide into new cancer cells, a targeted treatment is designed to turn off a signal that tells cells to divide or to delay cell death.

Inside a cancer cell

Cells are the building blocks of every tissue in your body. There are many different types of cells, such as blood cells, brain cells, and skin cells, which have specific functions. Cancer begins when healthy cells change and grow uncontrollably, forming a mass called a tumor. A tumor can be benign (noncancerous) or malignant (cancerous, meaning it can spread to other parts of the body). The change from a normal cell to a cancerous one is largely the result of specific mutations to genes that control cell division or delay the normal processes by which cells die. Learn more about the genetics of cancer.

By studying cancer cells and how they react to their environment, researchers are finding that specific gene mutations are related to the development of specific cancers. With this knowledge, they can develop drugs that correct or modify the changes in the cancer cell to stop or slow the growth of cancer.

For example, researchers learned that about 20% to 25% of all breast cancers have too much of a protein called human epidermal growth factor receptor 2 (HER2). A drug called trastuzumab (Herceptin) treats cancer by blocking HER2, but it is only effective for people with breast cancer whose tumors have HER2.

Outside of the cancer cell

Groups of cancer cells don't exist alone. The tumor is part of a larger network of tissues, lymph (a colorless fluid that carries lymphocytes, which are specialized white blood cells), and blood vessels. When cancer spreads from one part of the body to another, it is because of cancer cells that have broken off from the main tumor and traveled through the blood or lymph system. Nearby blood vessels help feed the growing tumor.

In fact, one of the more successful approaches has been to target angiogenesis, the new blood vessel growth around a tumor. Targeted therapies such as bevacizumab (Avastin), lenalidomide (Revlimid), sorafenib (Nexavar), sunitinib (Sutent), and thalidomide (Thalomid) interfere with angiogenesis. Read more about angiogenesis and angiogenesis inhibitors to treat cancer.

Types of targeted treatments

Targeted treatments can be classified in the following ways:

• Monoclonal antibodies are substances that are made in the laboratory to block a specific target on the outside of cancer cells. Think of this as placing a protective plastic plug into an electrical socket to prevent electricity from flowing. These drugs are usually given intravenously (IV) because they are large compounds that are not absorbed well by the body. Examples include alemtuzumab (Campath-1H), bevacizumab, cetuximab (Erbitux), panitumumab (Vectibix), pertuzumab (Omnitarg), rituximab (Rituxan), and trastuzumab. In one instance, a drug called tositumomab (Bexxar) is a monoclonal antibody used to deliver radiation to the tumor.
• Oral small molecules are given in the form of a pill that a patient takes by mouth because the body absorbs them better than monoclonal antibodies. These drugs usually block cancer processes in the inside of a cancer cell. Examples include dasatinib (Sprycel), erlotinib (Tarceva), gefitinib (Iressa), imatinib (Gleevec), lapatinib (Tykerb), nilotinib (Tasigna), sorafenib, sunitinib, and temsirolimus (Torisel).
• Proteasome inhibitors interfere with specialized proteins called enzymes that break down other proteins in the cell. A multiple myeloma drug, bortezomib (Velcade), is an example of this drug and is given by injection.

Matching patient to treatment

Recent studies show that not all tumors have the same targets, which may explain why a targeted treatment doesn't work for each person. Because many of these treatments have some degree of side effects and because the cost of these treatments can be expensive, doctors are making efforts to match each patient to the most effective treatment whenever possible. Learn more about personalized cancer medicine.

One example is HER2 and breast cancer. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists recommend that all people with invasive breast cancer have their tumors tested for HER2. If a person's tumor has HER2, then treatment with drugs that target HER2, such as trastuzumab and lapatinib, are likely to be effective. But, people whose tumors do not have HER2 do not benefit from these drugs. In other words, a targeted treatment doesn't work if the tumor doesn't have the target.

A similar situation exists for a gene called KRAS (pronounced kay-rass). This gene is mutated in about 40% of colorectal cancers. When this happens, the targeted therapies of cetuximab and panitumumab don't work. ASCO recommends that patients with metastatic colorectal cancer have their tumors tested for KRAS mutations, so that doctors can give their patients the most effective treatment and not expose patients to unnecessary side effects.

Challenges of targeted treatments

Although the idea of targeting a drug to a tumor seems straightforward, problems can arise when using this approach. For example, the target in the cancer cell may turn out not to be important, and the drug won't work. Or, the cancer may become resistant to the treatment, meaning it no longer works, even if it has previously. Finally, these drugs may still cause serious side effects, although the side effects are usually different than those seen with traditional chemotherapy. For instance, angiogenesis inhibitors are often associated with high blood pressure.

Although the development of targeted treatments is a breakthrough in cancer treatment, few cancers are cured with these drugs alone. With few exceptions, patients with cancer are still treated with a combination of surgery, chemotherapy, radiation therapy, and/or hormonal therapy. As doctors gain more knowledge about specific changes in the cancer cell, more of these targeted treatments can be tailored to each person. Find the latest research on targeted therapy as presented at the ASCO Annual Meeting or in the Cancer.Net Guides to Cancer.

More Information

Understanding Pharmacogenomics

Additional Resources

DiscoverMI.org: Molecular Radiotherapy (MRT)

Last Updated: May 25, 2011