Page 24 Complete Your CE Test Online - Click Here Genetics, genomics, and treatment with targeted therapy Many targeted therapies depend on testing for tumor genetics before the treatment starts. For example, one well-known test involves looking at estrogen receptors in breast cancer to determine whether antiestrogen compounds can help with treatment of that particular woman’s cancer. Another example from breast cancer is the overexpression of human epidermal growth factor receptors (HER2), indicating that the patient will likely benefit from using trastuzumab. Some call this tumor profiling, and others call it individualized or personalized therapy. Tumor tissue testing is different from testing germline mutations, which are present in all the body’s cells and can be done with a blood sample. Tumor testing requires a sample of the cancerous tissue and is often done using part of the biopsy sample. This kind of testing can show whether certain targeted drugs can help stop cancer growth. Targeted therapy can cause side effects Side effects of targeted therapy depend on the drug and the patient’s responses. The most common side effects of targeted therapy are diarrhea and elevated liver function tests. Other side effects might include bleeding and delayed wound healing, high blood pressure, fatigue, mucositis, nail changes, loss of hair color, and rash or dry skin. Very rarely, a fistula might form through the wall of the esophagus, stomach, small intestine, large bowel, rectum, or gallbladder. Many of these side effects are treatable, and most of them fade after treatment ends. Fistulas and severe diarrhea, although rare, can be life-threatening. Immunotherapy Cancer is able to grow and evolve in part because cells develop ways to elude the immune system. Immunotherapy is a type of cancer treatment that helps the immune system fight cancer. The immune system consists of lymphocytes made by the bone marrow; the thymus; lymph nodes; spleen; tonsils; and specialized tissues in the mucous membranes of the nose, bronchi, gut, urinary tract, and other tissues. Immunotherapy is a type of biological therapy that uses substances made from living organisms to treat cancer. Types of immunotherapy Many different types of immunotherapy are used to treat cancer. Following is a rundown. Monoclonal antibodies are drugs designed to bind to specific targets in the body. They can cause an immune response that destroys cancer cells (such as pembrolizumab or nivolumab) or helps to stop them from growing (such as trastuzumab). Other types of monoclonal antibodies mark cancer cells so the immune system can destroy them, which is called targeted therapy (see “Targeted Therapy”). Adoptive cell transfer is a treatment that attempts to boost the ability of T cells (T-lymphocytes) to fight cancer. Researchers take T cells from the patient, isolate the T cells that are most active against the cancer, or modify the genes in them to make them better able to find and destroy the cancer cells. Researchers then grow large batches of these T cells in the lab over the course of two to eight weeks. The T cells that were grown in the lab are then introduced into the patient. Cytokines are proteins that play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer. The two main types of cytokines used to treat cancer are called interferons (e.g., interferon alfa) and interleukins (e.g., IL-2). There are also drugs, similar to cytokines but do not occur naturally, like thalidomide and lenalidomide, that boost the immune system. Treatment vaccines work against cancer by boosting the immune response to cancer cells. The treatment vaccines are different from the ones that help prevent disease. An example of this is sipuleucel-T, which is used to treat advanced prostate cancer. Bacillus Calmette-Guérin (BCG) is an immunotherapy that is used to treat bladder cancer. It is a weakened form of the bacterium that causes tuberculosis. When injected directly into the bladder, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer. Immunotherapy may be given via IV, orally, topically (for very early skin cancer, like imiquimod cream), or intravesically, and it is typically given on an outpatient basis every day, week, or month. Some immunotherapies are given in cycles. Immunotherapy is not yet as widely used as surgery, chemotherapy, and radiation therapy. However, immunotherapies have been approved to treat people with many types of cancer, and many others are being studied in clinical trials. Immunotherapy can cause side effects The side effects depend on the type of immunotherapy. Rarely, immunotherapies may also cause severe or even fatal allergic reactions. The most common side effects are skin reactions at the needle site, such as pain, swelling, redness, or itching. They can also cause flu-like symptoms: ● ● Fever. ● ● Chills. ● ● Weakness. ● ● Dizziness. ● ● Nausea or vomiting. ● ● Muscle or joint aches. ● ● Fatigue. ● ● Headache. ● ● Trouble breathing. ● ● Low or high blood pressure. Other side effects include the following: ● ● Swelling. ● ● Weight gain from fluid retention. ● ● Palpitations. ● ● Sinus congestion. ● ● Diarrhea. ● ● Risk of infection. Drug interactions and effects in cancer treatment CYP 450 enzymes: A clinically important system As mentioned in the “Pretreatment Assessment” section, most health professionals have heard of the CYP 450 drug interaction issue but many are not sure how it works. CYP 450 enzymes are mostly produced in the liver, but the gut produces them too. About 10 of these enzymes can affect drugs in a significant way. These enzymes help to metabolize many drugs so that they can be inactivated and excreted. It is important to know that not only do the enzymes affect certain drugs but also some drugs can affect the production of the enzymes. This means that one drug can indirectly affect another in significant ways. A drug that requires a certain enzyme to be metabolized is called a substrate of that enzyme. For example, alprazolam (Xanax) is a substrate of enzyme CYP 3A4, which is required to metabolize it. The half-life of this drug is usually about 11 hours (but can vary between 6 and 27 hours). This is typically fairly constant in each person, all other things being equal. However, if a person is taking an inducer of CYP 3A4, the alprazolam could leave the body very quickly. If the person is taking an inhibitor of CYP 3A4, the alprazolam blood level could climb much higher and last much longer in the body. Grapefruit and starfruit also act as 3A4 inhibitors, which means that patients taking alprazolam can intensify and extend the activity of this benzodiazepine if they drink grapefruit juice. Although this may be a problem, it can be a more severe issue if they are taking a 3A4 substrate such as vincristine or imatinib (Gleevec), which might result in more unpredictable and severe toxicities. Following are the most important of these enzymes: ● ● CYP 1A2. ● ● CYP 2B6. ● ● CYP 2C8. ● ● CYP 2C9. ● ● CYP 2C19. ● ● CYP 2D6. ● ● CYP 2E1. ● ● CYP 3A4, 5, 7. (These are typically grouped Because they are related and on the same gene; sometimes the whole group is often called simply CYP 3A or the CYP 3A family.)