Targeted Therapies
The goal of chemotherapy is to kill cancer cells that grow and divide rapidly. It also affects normal cells that are also fast growing (e.g., cells in the skin, lining of the digestive tract, hair follicles), which can cause unwanted side effects. To reduce damage to normal cells, newer drugs called targeted therapies interfere with the ways that cancer cells function. These processes include:
- New blood vessel formation (angiogenesis)
- Cancer cells rely on new blood vessels to supply them with oxygen and nutrients. Drugs that block angiogenesis starve cells of their blood supply, which helps to slow or stop tumor growth. These drugs also seem to make traditional chemotherapies more effective.
- Stimulation from growth signals
- Cancer cells may rely on signals that tell them to grow or divide uncontrollably. Drugs that block these signals may help to slow or stop tumor growth.
Most targeted therapies are either monoclonal antibodies or small-molecule drugs.
Monoclonal antibodies are proteins that attach to substances called receptors on the surface of the cell and block signals that tell the cell what to do. They can also be used alone to target defects in the cancer cells or make the cancer cells more receptive to the body’s immune system. Monoclonal antibodies can also carry other drugs or substances directly to a tumor.
- Bevacizumab (Avastin)* was approved in 2004 for treating non-small cell lung cancer (NSCLC) that is not squamous cell carcinoma. It is frequently given with traditional chemotherapy. Avastin should not be used to treat squamous cell lung cancer because in clinical trials, those with squamous cell had many more life-threatening and fatal side effects from the drug.
Small-molecule drugs can get inside the cell and stop the cell from functioning normally, which usually causes it to die. Tyrosine kinase inhibitors (TKIs) are small-molecule drugs that interfere with cell communication and growth. Several TKIs are being studied for use in lung cancer, and one is widely available after having been approved in 2004.
- Erlotinib (Tarceva) was approved for use in 2004. It is most effective in treating non-small cell lung cancer when an EGFR mutation is present. This mutation is most frequently present in women, never smokers, and people of Southeast Asian origin. It is also most commonly found in adenocarcinoma, a type of NSCLC.
- Gefitinib (Iressa) was approved in the US in May 2003 but removed in June 2005 after studies showed it did not help the majority of people to live longer. Like Tarceva, Iressa targets the EGFR mutation. Iressa is still available to patients who received benefit from the drug at the time the US approval was removed. It remains an approved treatment for lung cancer in over 30 countries and continues to be studied in clinical trials in the US.
- Crizotinib (Xalkori) was approved in September 2011. It targets the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) mutation. This mutation is only present in about 4-5% of people with NSCLC, primarily those diagnosed with adenocarcinoma. It is more common in men and never smokers. The drug has shown dramatic results in patients with this mutation.
*On February 14, 2012 the makers of Avastin, Genentech, issued a statement to warn the public that a counterfeit product labeled as Avastin has been distributed in the United States. Information with the lot numbers for the counterfeit product has been distributed to healthcare providers. If you have been prescribed Avastin and would like to know more, please see this statement on the Genentech website and talk with your healthcare team.