Targeted Therapy: The Basics
What is targeted therapy?
Targeted therapy is a type of cancer treatment. Chemotherapy works by killing cells that divide rapidly, which includes cancer cells, but also many types of healthy cells (hair, GI tract, blood cells, etc). Targeted therapies work by targeting something specific to a cancer cell, which allow the medication to kill cancer cells while preserving the health of most normal cells. Sometimes the “target” is found on a certain type of healthy cells and side effects occur as a result. Targeted therapy is sometimes called precision medicine or personalized medicine, as one person’s cancer may be treated differently than another based on the targets found on their tumor. Immunotherapy is one type of targeted therapy.
Targeted therapy medications work by inhibiting molecular targets in the cancer cell that contribute to the growth, spread, and progression of cancer. In many cases, your healthcare provider will have to test your tumor to determine if a specific target is present. Even though individuals may have the same type of cancer, they may not have the same molecular targets to target. Thus, the same targeted treatment doesn’t work for everyone with that type of cancer. In addition, just because the target is present, doesn’t mean the tumor will respond to the targeted therapy.
Common molecular targets (mutations) that are treated with targeted therapies include HER2, EGFR, KRAS, VEGF, ALK, JAK 1 and 2, BTK and BRAF. Your healthcare team may test you for these mutations, depending on your cancer type and if a mutation is known in that cancer type.
Targeted therapies are currently FDA approved for the treatment of many cancers including, breast, colorectal, lung, thyroid, and prostate cancers, lymphoma, leukemia, myeloma, CLL, and melanoma. Targeted therapy may be given alone or in combination with chemotherapy, radiation and/or surgery. Clinical trials studying other potential targeted therapies are in progress for many other cancer types.
What are the different types of targeted therapies?
Small molecule drugs
- Kinase Inhibitors: The growth of cells in our body are controlled by growth factors, which attach themselves to the surface of cells, triggering a series of chemical reactions that allow the cell to grow and divide. Cancer cells do not function properly and are able to grow and divide even when growth factors are not present. Kinase inhibitors work by blocking signals within cancer cells, preventing a step necessary for the cell to grow and divide.
Angiogenesis Inhibitors: Angiogenesis is the development of blood vessels to supply the tumor with nutrients it needs to grow. These medications work to block the formation of this blood supply and cut off the tumor's source of nutrients.
- Some kinase inhibitors also act as angiogenesis inhibitors (examples: sorafenib (Nexavar), sunitinib (Sutent®), everolimus (Afinitor®). Examples of angiogenesis inhibitors include: ziv-aflibercept (Zaltrap®), lenalidomide (Revlimid®) and vandetanib (Caprelsa®).
Monoclonal antibodies: These laboratory-created antibodies that target a specific antigen (protein) work in a few different ways. They can target a specific cell (the cancer cell), sending a message to the immune system to destroy the targeted cell. Some monoclonal antibodies also impede the growth of cancer cells by interfering with functions necessary for cell growth.
- Examples of monoclonal antibodies are: bevacizumab (Avastin®), trastuzumab (Herceptin®) and denosumab (Xgeva®, Prolia®).
- Radioimmunotherapy: This is a combination of a monoclonal antibody and a radiation source, which permits radiation to be delivered directly to the targeted cells, but often in lower doses and over a longer period of time. An example is ibritumomab tiuxetan (Zevalin®).
How are targeted therapies given?
Some targeted therapies are given by pill, others are given by vein (IV). Be sure to pay attention to storage and handling recommendations for oral medications. It is also extremely important that you take your oral medications as prescribed.
Some of these oral medications are very expensive. Be sure to talk with your healthcare team if you can’t afford your medication, as assistance may be available.
What are the side effects of targeted therapies?
There are side effects to targeted therapies. Not everyone will experience these side effects and the severity of the side effects can vary from person to person. Be sure to talk with your healthcare team about side effects you may be experiencing. Do not stop taking your oral medications due to side effects without talking to your healthcare team.
Some targeted therapies impact the skin, causing an acne like rash or other skin changes. These are not the same as experiencing an allergy to the medication, but a direct effect of the medication. These skin changes happen in particular with EGFR and VEGF targeted therapies as these medications can also impact skin cells.
Skin side effects can exhibit in many different ways including, a sunburn like sensation (not necessarily appearance); your skin may feel irritated and angry, be sensitivity to sunlight, develop a rash, dry skin, hair loss or changes to hair texture, hand-foot syndrome, and other nail and skin changes.
Because many of these drugs are relatively new, we don’t know a lot about their potential for long term side effects. Be sure to talk with your healthcare team about fertility preservation before starting any targeted therapy, as these medications may impact your future ability to have a child. Certain targeted therapies like thalidomide and lenalidomide can cause serious birth defects and have special programs in place to educate patients and encourage safe distribution to patients of child bearing age.
Other side effects that patients on targeted therapies will be monitored for include problems with wound healing, blood clotting, high blood pressure and gastrointestinal (GI) perforation.
It is possible that over time, you may build up a resistance to the targeted medication you are receiving. This may happen more frequently when targeted therapy is the only therapy being received.
How will I know if targeted therapy is working for me?
Your healthcare team will continue to monitor your disease closely throughout your treatment. You will have regular blood and imaging (CT scan, PET scan) tests that will tell how your body is responding to treatment.
Resources for More Information
- American Cancer Society: Targeted Therapy http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/targetedtherapy/index
- National Cancer Institute: Targeted Therapy Fact Sheet http://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet
- American Society of Clinical Oncology (ASCO): Understanding Targeted Therapy http://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-targeted-therapy
Fabbro, D., Cowan-Jacob, S. W., Möbitz, H., & Martiny-Baron, G. (2012). Targeting cancer with small-molecular-weight kinase inhibitors. Kinase Inhibitors: Methods and Protocols, 1-34.
Gainor, J. F., & Shaw, A. T. (2013). Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. Journal of Clinical Oncology, 31(31), 3987-3996.
Groenendijk, Floris H. et al. (2014). Drug resistance to targeted therapies: Déjà vu all over again. Molecular Oncology, 8(6) 1067 – 1083.
Helena, A. Y., Riely, G. J., & Lovly, C. M. (2014). Therapeutic strategies utilized in the setting of acquired resistance to EGFR tyrosine kinase inhibitors. Clinical Cancer Research, 20(23), 5898-5907.
Hojjat-Farsangi, M. (2014). Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies. International Journal of Molecular Cciences, 15(8), 13768-13801.
Levitzki, A. (2013). Tyrosine kinase inhibitors: views of selectivity, sensitivity, and clinical performance. Annual Review of Pharmacology and Toxicology, 53, 161-185.
Licht, J. D., Shortt, J., & Johnstone, R. (2014). From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. Cancer Cell, 25(1), 9-11.
Partridge, A. H., Rumble, R. B., Carey, L. A., Come, S. E., Davidson, N. E., Di Leo, A., ... & Brundage, S. B. (2014). Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2–negative (or unknown) advanced breast cancer: American Society of Clinical Oncology clinical practice guideline. Journal of Clinical Oncology, JCO-2014.
Wu, P., Nielsen, T. E., & Clausen, M. H. (2015). FDA-approved small-molecule kinase inhibitors. Trends in pharmacological sciences, 36(7), 422-439.
Zaytseva, Y. Y., Valentino, J. D., Gulhati, P., & Evers, B. M. (2012). mTOR inhibitors in cancer therapy. Cancer Letters, 319(1), 1-7.
Zhang, J., Yang, P. L., & Gray, N. S. (2009). Targeting cancer with small molecule kinase inhibitors. Nature Reviews Cancer, 9(1), 28-39.