Targeted therapy uses medications that more precisely target cancer cells and avoid hurting healthy tissue. The OHSU Knight Cancer Institute is a world leader in developing targeted therapies and in making them available to more patients.

• Dr. Brian Druker, physician and scientist of the Knight Cancer Institute, helped launch the entire field of targeted therapy with the leukemia drug imatinib (Gleevec).
• Our researchers have built a new clinical trials strategy, called SMMART, to stop tumors before they can adapt to resist medications.
• Through clinical trials, we are developing treatments for cancers such as osteosarcoma and acute myeloid leukemia (AML) that otherwise have limited options.

Understanding targeted therapy

What is targeted therapy? Targeted therapy medications act on specific proteins, genes or enzymes to stop cancer cells from growing or surviving.

How targeted therapy works: Targeted therapy medications block cancer signals. They can block or turn off signals that make cancer cells grow, for example, or they can tell the cells to self-destruct. They do this by acting on a “target” such as a protein on a cancer cell.

Finding targets: Often, the patient’s tumor is tested to see if it contains any of the known targets that we can match with a medication. Your doctor may do a biopsy to remove a piece of the tumor with a hollow needle or surgery.

How targeted therapy is given: Medications may be given as pills, by IV drip or with an injection under the skin.

Benefits of targeted therapy:

• Targeted therapy medications act on a protein or gene that only cancer cells have. It mostly leaves healthy cells alone. Traditional chemotherapy, on the other hand, attacks fast-dividing cells. That means it kills cancer cells but can also harm normal fast-dividing cells, such as the ones in hair roots.
• Targeted therapy is an option for some otherwise difficult-to-treat cancers.

Limits of targeted therapy:

• It can treat only some cancers.
• Most people still need other treatments, such as surgery, chemotherapy, radiation therapy and/or hormone therapy.
• Most tumors develop resistance. The cancer cells adapt and find new ways to multiply and spread. To make the next leap, Knight Cancer Institute doctors and scientists are working to develop combination treatments that block more than one cancer pathway at the same time.

Targeted therapy by cancer type

Here are examples of targeted therapy, all available at the Knight Cancer Institute.

Breast cancer

Some breast cancers make a large amount of a protein called HER2 (human epidermal growth factor receptor 2), which helps drive tumor growth. The Food and Drug Administration has approved many targeted therapy medications to treat HER2-positive breast cancers.

Colorectal cancer

Several kinds of targeted therapy are approved for colorectal cancer.

• Some medications target a protein called VEGF, which some tumors use to grow new blood vessels.
• Some medications target EGFR, a protein overproduced by some tumors to drive growth.
• Medications called BRAF inhibitors can be used to treat colorectal cancers that have mutated BRAF genes.
• A medication called Stivarga (regorafenib) blocks kinase proteins that help tumor cells grow. It’s used to treat advanced colorectal cancer, usually when other medications aren’t helping.

Leukemia and lymphoma

• Gleevec quickly became the gold standard for treating chronic myeloid leukemia (CML). It targets a mutant protein that drives cancer transformation in CML.
• Second- and third-generation tyrosine kinase inhibitors improve outcomes when CML becomes resistant to Gleevec.
• Targeted therapies that block the enzyme that drives the overproduction of B cells have improved outcomes for some people with lymphoma or with some B-cell leukemias.
• Targeted therapies have been developed in recent years to fight acute myeloid leukemia (AML), a hard-to-treat blood cancer. They include venetoclax (Venclexta), which takes aim at cancer cells’ ability to evade cell death.
• Venetoclax is also among targeted therapies for chronic lymphocytic leukemia (CLL). Other therapies include monoclonal antibodies (also a form of immunotherapy) that target a certain protein on the surface of blood cells.

Learn more about treatment at OHSU for leukemia and lymphoma.

Lung cancer

The FDA has approved a wide variety of targeted therapy medications to treat non-small cell lung cancer, the most common type. In some cases, targeted therapy replaces chemotherapy as the first treatment. Doctors choose medications based on the features of each patient’s tumor.

Melanoma

About half of melanomas have a mutation in the BRAF gene that helps the cancer grow. Medications that target the mutated BRAF protein include:

• Zelboraf (vemurafenib)
• Tafinlar (dabrafenib)
• Braftovi (encorafenib)

These medications can shrink or slow the growth of tumors in some people whose melanoma has spread. They can be used in combination with other medications that target a protein called MEK.

Prostate cancer

Two targeted therapies, Rubraca (rucaparib) and Lynparza (olaparib), are approved to treat prostate cancer. These medications, called PARP inhibitors, block an enzyme called PARP that cancer cells may use to repair themselves.

The medications are used to treat advanced, hormone-resistant prostate cancers with specific gene mutations. Your doctor might test your tumor and your blood or saliva to see if you have one of the mutations.

Clinical trials and research

Cancer patients at OHSU have access to the latest targeted therapy advances, including experimental treatments that are not available anywhere else in the region. Knight Cancer Institute doctors are leading the development of new targeted therapies.

Clinical trials

• We offer clinical trials that give eligible patients a chance to try experimental treatments. Your care team will talk with you about whether a trial is right for you.
• The Knight Cancer Institute has developed a revolutionary clinical trials platform, called SMMART, to stop tumors before they can become medication-resistant. The new platform makes it possible to:
  • Study each person’s tumor in detail.
  • Track how cancer cells change in response to treatment.
  • Use the information to combine medications, like a one-two punch, before the tumor can adapt.
  • Tailor each combination to the individual patient.

Research

• The Beat AML study is paving the way to targeted therapies that stop acute myeloid leukemia. Study volunteers who received the precision medicine approach showed better overall survival compared with those who opted for standard care. Dr. Druker helped plan and develop the trial, and OHSU was among the top four sites enrolling subjects.
• OHSU researchers are working to uncover why AML cancer cells sometimes develop resistance to targeted therapies. This could help doctors identify new ways to fight the cancer or to outwit its ability to resist therapy.

Learn more

• Targeted Therapy, American Cancer Society
• How Targeted Therapies are Used to Treat Cancer, American Cancer Society
• Targeted Therapy to Treat Cancer, National Cancer Institute
• Targeted Therapy Drugs for Acute Myeloid Leukemia (AML), American Cancer Society
• Targeted Therapy Drugs for Chronic Lymphocytic Leukemia, American Cancer Society
• Monoclonal Antibodies for Chronic Lymphocytic Leukemia, American Cancer Society
• Targeted Therapies for Chronic Myeloid Leukemia, American Cancer Society
• Targeted Therapy Drugs for Non-Hodgkin Lymphoma, American Cancer Society
• Understanding Cancer Clinical Trials, OHSU Knight Cancer Institute