A) Principles of targeted therapy for treatment of cancer. B) Enumerate various agents, their targets and indications for use of targeted therapy in surgical practice

June 2015

https://sites.google.com/site/surgerypaper/2015/targeted-therapy-for-treatment-of-cancer




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Understanding Targeted Therapy

Approved by the Cancer.Net Editorial Board, 01/2019

Targeted therapy is a cancer treatment that uses drugs. But it is different from traditional chemotherapy, which also uses drugs to treat cancer. Targeted therapy works by targeting the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. These genes and proteins are found in cancer cells or in cells related to cancer growth, like blood vessel cells.

Doctors often use targeted therapy with chemotherapy and other treatments. The U.S. Food and Drug Administration (FDA) has approved targeted therapies for many types of cancer. Scientists are also testing drugs for new cancer targets.

The “targets” of targeted therapy

It is helpful to know how cancer cells grow in order to better understand how targeted therapy works. Cells make up every tissue in your body. There are many different cell types, such as blood cells, brain cells, and skin cells. Each type has a specific function. Cancer starts when certain genes in healthy cells change. This change is called a mutation.

Genes tell cells how to make proteins that keep the cell working. If the genes change, these proteins change, too. This makes cells divide abnormally or live too long. When this happens, the cells grow out of control and form a tumor. Learn more about the genetics of cancer.

Researchers are learning that specific gene changes take place in certain cancers. So they are developing drugs that target the changes. The drugs can:

    Block or turn off signals that tell cancer cells to grow and divide

    Keep cells from living longer than normal

    Destroy the cancer cells

Types of targeted therapy

There are several types of targeted therapy:

    Monoclonal antibodies. Drugs called “monoclonal antibodies” block a specific target on the outside of cancer cells and/or the target might be in the area around the cancer. These drugs work like a plastic cover you put in an electric socket. The plug keeps electricity from flowing out of the socket.

    Drugs called “monoclonal antibodies” block a specific target on the outside of cancer cells and/or the target might be in the area around the cancer. These drugs work like a plastic

    Monoclonal antibodies can also send toxic substances directly to cancer cells. For example, they can help chemotherapy and radiation therapy get to cancer cells better. You usually get these drugs injected into a vein, or "intravenously" (IV).

    Small-molecule drugs. Drugs called “small-molecule drugs”can block the process that helps cancer cells multiply and spread. These drugs are usually taken as pills. Angiogenesis inhibitors are an example of this type of targeted therapy. These drugs keep tissue around the tumor from making blood vessels. Angiogenesis is the name for making new blood vessels. A tumor needs blood vessels to bring it nutrients. The nutrients help it grow and spread. Anti-angiogenesis therapies starve the tumor by keeping new blood vessels from forming.

Matching a patient to a treatment

Studies show that not all tumors have the same targets. So the same targeted treatment will not work for everyone. For example, a gene called KRAS (pronounced kay-rass) controls the growth and spread of a tumor. About 40% of colorectal cancers have this gene mutation. When this happens, the targeted therapies cetuximab (Erbitux) and panitumumab (Vectibix) are not effective. If you have colorectal cancer, it is helpful to be tested for the KRAS mutation. This would help your doctor give you the most effective treatment. It also protects you from unnecessary side effects.

Some treatments, called "tumor-agnostic" or "site-agnostic treatments," are not specific to a certain type of cancer. Instead, they focus on a specific genetic change and are used to treat tumors anywhere in the body. A tumor may also be tested for other genetic changes, including BRAF and HER2. These markers do not have FDA-approved targeted therapies yet, but there may be opportunities in clinical trials that are studying these changes. Learn more about tumor-agnostic treatments.

Recently, the FDA approved larotrectinib (Vitrakvi) as a type of targeted therapy that focuses on a specific genetic change called an NTRK fusion. This type of genetic change is found in a range of cancers. Larotrectinib is approved for these cancers that are metastatic or cannot be removed with surgery and have worsened with other treatments.

Your doctor might order tests to learn about the genes, proteins, and other factors in your tumor. This helps find the most effective treatment. Many targeted therapies cause side effects. Also, they can be expensive. So, doctors try to match every tumor to the best possible treatment.

Examples of targeted therapies

Below are a few examples of targeted therapies. Ask your health care team for more information.

    Breast cancer. About 20% to 25% of all breast cancers have too much of a protein called human epidermal growth factor receptor 2 (HER2, pronounced her-too). This protein makes tumor cells grow. If the cancer is HER2 positive, several targeted therapies are available. Learn more about targeted therapy for breast cancer.

    Colorectal cancer. Colorectal cancers often make too much of a protein called epidermal growth factor receptor (EGFR). Drugs that block EGFR may help stop or slow cancer growth. These cancers have no mutation in the KRAS gene. Another option is a drug that blocks vascular endothelial growth factor (VEGF, pronounced vedge-eff). This protein helps make new blood vessels. Learn more about targeted therapy for colorectal cancer.

    Lung cancer. Drugs that block the protein called EGFR may stop or slow lung cancer growth. This may be more likely if the EGFR has certain mutations. Drugs are also available for lung cancer with mutations in the ALK and ROS genes. Doctors can also use angiogenesis inhibitors for certain lung cancers. Learn more about targeted therapy for non-small cell lung cancer.

    Melanoma. About half of melanomas have a mutation in the BRAF gene (pronounced bee-raff). Researchers know specific BRAF mutations make good drug targets. So the FDA has approved several BRAF inhibitors. These drugs can be dangerous if you do not have the BRAF mutation. Learn more about targeted therapy for melanoma.

The list above does not include every targeted therapy. Researchers are studying many new targets and drugs. You can learn more about targeted therapy in each cancer-specific section on Cancer.Net in the Treatment Options and Latest Research pages. You can also learn more about the latest targeted therapy research on the Cancer.Net blog.

It may seem simple to use a drug that works on your specific cancer. But targeted therapy is complex and not always effective. It is important to remember that:

    A targeted treatment will not work if the tumor does not have the target.

    Having the target does not mean the tumor will respond to the drug.

    The response to treatment may be temporary.

For example, the target may not be as important as doctors first thought. So the drug may not help much. Or the drug might work at first but then stop working. Finally, targeted therapy drugs may cause serious side effects. These are usually different from traditional chemotherapy effects. For example, people receiving targeted therapy often have skin, hair, nail, or eye problems.

Targeted therapy is an important type of cancer treatment. But so far, doctors can only get rid of a few cancers using only these drugs. Most people also need surgery, chemotherapy, radiation therapy, or hormone therapy. Researchers will develop more targeted drugs as they learn more about specific changes in cancer cells.