Tyrosine Kinase Inhibitors

What are tyrosine kinase inhibitors (TKIs)?

Tyrosine kinase inhibitors (TKIs) are targeted therapies that treat many kinds of cancer. They block certain substances in cancerous cells that manage how fast the cells grow and divide. Tyrosine kinase inhibitors can’t cure cancer, but they can put cancer into long-term remission or help people with certain cancers to live longer.

How do tyrosine kinase inhibitors work?

Tyrosine kinase inhibitors disrupt the process that manages how your cells grow and divide. That process involves:

• Growth factors: Chemicals that control cell growth.
• Tyrosine kinases: Enzymes inside your cells that control cell division.

Growth factors flip the switch that activates tyrosine kinases. In turn, tyrosine kinases signal cells so they start to divide. The cells continue dividing until tyrosine kinases turn off. Normal tyrosine kinases turn on and off as needed.

Treatment for chronic myeloid leukemia (CML) is a good example of how TKIs work. CML is a blood cancer that starts in the blood-forming myeloid cells (stem cells) in your bone marrow. When myeloid cells mutate, they make abnormal tyrosine kinase enzymes that turn on when the growth factor flips the switch. They never turn off.

Without an “off” switch, myeloid cells in your bone marrow divide and multiply uncontrollably, making it hard for your bone marrow to make other blood cells and platelets your body needs. Tyrosine kinase inhibitors treat CML by flipping the “on” switch to “off,” blocking abnormal enzyme signals that make cancerous cells divide.

What cancers are treated with tyrosine kinase inhibitors?

Tyrosine kinase inhibitors treat several kinds of cancer, including:

• HER2-positive breast cancer.
• Chronic lymphocytic leukemia.
• Gastrointestinal stromal tumors.
• Kidney cancer.
• Waldenstrom macroglobulinemia.
• Non-small cell lung cancer.
• Melanoma.

How many tyrosine kinase inhibitors can treat cancer?

As of November 2022, the U.S. Food and Drug Administration has approved 50 tyrosine kinase inhibitors to treat tumors including lung, breast and colon cancer, and eight drugs to treat blood cancers like leukemia. Four other medications treat both cancerous tumors and certain blood cancers. Imatinib (Gleevec®), the first FDA-approved tyrosine kinase inhibitor, treats seven types of cancer.

What happens during this treatment?

Tyrosine kinase inhibitors come in pill or liquid form. Depending on the cancer type and stage, people may take one or two pills or liquid medication daily.

How long will I need to take this medication?

That depends on your situation. For example, if you have chronic myeloid leukemia, you may take the medication for the rest of your life.

What are tyrosine kinase inhibitor side effects?

Tyrosine kinase inhibitors treat a wide range of cancers and cause an equally wide range of side effects. For example, one group of tyrosine kinase inhibitors targets cancers such as non-small lung cancer, breast, colorectal and pancreatic cancer. Those treatment side effects may range from mild skin rashes to life-threatening skin issues like Steven-Johnson syndrome/toxic epidermal necrosis. Another group of TKIs that target non-small lung cancer and colorectal cancer may cause cardiovascular issues like high blood pressure (hypertension) and proteinuria.

Side effects vary based on the specific TKI and may include:

• Fatigue.
• Fever.
• Weight loss/weight gain.

If you’re receiving a tyrosine kinase inhibitor, ask your healthcare provider about specific treatment side effects.

What are the potential benefits of tyrosine kinase inhibitor treatment?

Tyrosine kinase inhibitors are targeted therapies for cancer and other conditions. Like all targeted therapies, its major benefit is killing cancer cells without damaging healthy cells. Tyrosine kinase inhibitors may be an alternative when other cancer treatments aren’t effective.

Is this treatment successful?

Tyrosine kinase inhibitors are effective treatments for many kinds of cancer. In general, tyrosine kinase inhibitors slow cancer down and help people live longer. For chronic myeloid leukemia, for example, this treatment turned a life-threatening disease into a chronic illness that medication can manage. They’re also effective treatments for some cancers that come back after treatment (cancer recurrence) or cancer that’s spreading (metastatic cancer).

What are the risks or complications of this treatment?

Tyrosine kinase inhibitors work well against many kinds of cancer. But over time, some cancers change. When that happens, the treatment that stopped the cancer growth is no longer working.

Is there anything I can do to make this treatment easier on me?

Most cancer treatment is stressful and challenging, and tyrosine kinase inhibitors are no exception. Side effects may be mild. Rarely, they may be life-threatening. Knowing what to expect is one way you can make this treatment easier. Here are some other suggestions:

• Fatigue is a very common treatment side effect. Try to get as much sleep and rest as you can.
• Treatment may affect your appetite. Some people have trouble eating and lose weight. Others find they’re gaining weight. If you’re experiencing weight loss or weight gain, ask a nutritionist for help with meals and menu plans.
• Cancer treatment often disrupts your daily life. Finding ways to stay organized during treatment may reduce the impact that treatment may cause.
• Consider palliative care — specialized care that helps you manage symptoms and treatment side effects — so you can live more comfortably with a serious disease like cancer.

When should I call my healthcare provider?

As you go through treatment, your provider will discuss how it may affect you. They’ll also discuss any symptoms that may be signs treatment isn’t working or that the cancer’s spread.

A note from Cleveland Clinic

Tyrosine kinase inhibitors (TKIs) keep cancerous cells from growing and spreading. From a medical standpoint, tyrosine kinase inhibitors launched targeted therapy for cancer — therapy that targets cancerous cells without damaging or destroying healthy cells. For people with cancer, tyrosine kinase inhibitors represent additional ways to treat many kinds of cancer. These medications may not cure all kinds of cancer, but they’re helping many people with cancer to live longer and with good quality of life.