What Are Tyrosine Kinase Inhibitors?

Cancer treatments have dozens of names and acronyms associated with them. Each type of cancer generally responds to a different medication, and even within a cancer type, there are subtypes depending on the mutations present in a specific tumor. Tyrosine kinase inhibitors (TKIs) are a form of targeted therapy that are used to treat many types of leukemia, as well as solid tumors such as non-small cell lung cancer (NSCLC). Targeted therapies have become extremely common in cancer treatment, because they are able to identify and attack cancer cells while causing much less damage to healthy cells.

TKIs block the action of enzymes called tyrosine kinases. Tyrosine kinases are involved in multiple cell functions, including cell signaling, growth and division. When these enzymes are overactive or mutated, they can cause cells to grow uncontrollable (resulting in cancer). TKIs work by blocking these enzymes, which, in turn, stops cancer cells from growing and helps slow  the disease down dramatically in many cases.

TKIs are used both as an initial treatment method, as well as in cases of resistance when treating cancer. Initial treatments are the first-line therapy used on a patient to treat a disease. If the initial therapy fails to work on the patient, meaning the cancer doesn’t respond or the person isn’t able to tolerate the side effects, another treatment option is often prescribed. Certain TKIs, such as imatinib mesylate and dasatinib, are used as first and second-line therapies, while other medications, such as bosutinib and ponatinib, are used generally when patients have failed one of the front-line treatments. Second- and other later line therapies are often created to specifically overcome resistances created by one or more earlier lines of treatment.

Patients with NSCLC and certain forms of leukemia are the most common recipients of TKIs. Patients with chronic myeloid leukemia (CML) are often treated with TKIs, because they are able to target the abnormal ALK or BCR-ABL protein, respectively that causes uncontrollable cell growth. TKIs block the protein’s function causing cells to stop growing and die.

TKIs are also used to treat Philadelphia chromosome-positive acute lymphoblastic eukemia (Ph+ ALL). Before the discovery of TKIs in the early 2000s, patients diagnosed with Ph+ ALL had less than a 20% chance of long-term survival. When TKIs were introduced into treatment protocols alongside standard chemotherapy, the 5-year survival rate more than doubled. Recent studies have shown that second-generation TKIs are even more effective than their predecessors at combating this disease.

Patients with NSCLC are also treated with TKIs, particularly those who have a overactive or mutated forms of epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). Studies have shown that patients treated with EGFR TKIs have improved overall response rates and progression-free survival rates, as well as a better quality of life. Recently, second-generation TKIs targeting the T790M mutation of EGFR have become available for patients with this advanced form of NSCLC.