1. What are targeted cancer therapies?

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. Because scientists often call these molecules “molecular targets,” targeted cancer therapies are sometimes called “molecularly targeted drugs,” “molecularly targeted therapies,” or other similar names. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than other types of treatment, including chemotherapy and radiotherapy, and less harmful to normal cells.

Many targeted cancer therapies have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific types of cancer (see details in Questions 4 and 5). Others are being studied in clinical trials (research studies with people), and many more are in preclinical testing (research studies with animals).

Targeted cancer therapies are being studied for use alone, in combination with other targeted therapies, and in combination with other cancer treatments, such as chemotherapy.

2. How do targeted cancer therapies work?

Targeted cancer therapies interfere with cancer cell division (proliferation) and spread in different ways. Many of these therapies focus on proteins that are involved in cell signaling pathways, which form a complex communication system that governs basic cellular functions and activities, such as cell division, cell movement, how a cell responds to specific external stimuli, and even cell death. By blocking signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can help stop cancer progression and may induce cancer cell death through a process known as apoptosis. Other targeted therapies can cause cancer cell death directly, by specifically inducing apoptosis, or indirectly, by stimulating the immune system to recognize and destroy cancer cells and/or by delivering toxic substances to them.

The development of targeted therapies, therefore, requires the identification of good targets—that is, targets that are known to play a key role in cancer cell growth and survival. (It is for this reason that targeted therapies are often referred to as the product of “rational drug design.”)

For example, most cases of chronic myeloid leukemia (CML) are caused by the formation of a gene called BCR-ABL. This gene is formed when pieces of chromosome 9 and chromosome 22 break off and trade places. One of the changed chromosomes resulting from this switch contains part of the ABL gene from chromosome 9 coupled, or fused, to part of the BCR gene from chromosome 22. The protein normally produced by the ABL gene (Abl) is a signaling molecule that plays an important role in controlling cell proliferation and usually must interact with other signaling molecules to be active. However, Abl signaling is always active in the protein (Bcr-Abl) produced by the BCR-ABL fusion gene. This activity promotes the continuous proliferation of CML cells. Therefore, Bcr-Abl represents a good molecule to target.

3. How are targeted therapies developed?

Once a target has been identified, a therapy must be developed. Most targeted therapies are either small-molecule drugs or monoclonal antibodies. Small-molecule drugs are typically able to diffuse into cells and can act on targets that are found inside the cell. Most monoclonal antibodies usually cannot penetrate the cell’s plasma membrane and are directed against targets that are outside cells or on the cell surface.

Candidates for small-molecule drugs are usually identified in studies known as drug screens—laboratory tests that look at the effects of thousands of test compounds on a specific target, such as Bcr-Abl. The best candidates are then chemically modified to produce numerous closely related versions, and these are tested to identify the most effective and specific drugs.

Monoclonal antibodies, by contrast, are prepared first by immunizing animals (typically mice) with purified target molecules. The immunized animals will make many different types of antibodies against the target. Next, spleen cells, each of which makes only one type of antibody, are collected from the immunized animals and fused with myeloma cells. Cloning of these fusion cells results in cultures of cells that produce large amounts of a single type of antibody, or a monoclonal antibody. These antibodies are then tested to find the ones that react best with the target.

Before they can be used in humans, monoclonal antibodies are “humanized” by replacing as much of the non-human portion of the molecule as possible with human portions. This is done through genetic engineering. Humanizing is necessary to prevent the human immune system from recognizing the monoclonal antibody as “foreign” and destroying it before it has a chance to interact with and inactivate its target molecule.

4. What was the first target for targeted cancer therapy?

The first molecular target for targeted cancer therapy was the cellular receptor for the female sex hormone estrogen, which many breast cancers require for growth. When estrogen binds to the estrogen receptor (ER) inside cells, the resulting hormone-receptor complex activates the expression of specific genes, including genes involved in cell growth and proliferation. Research has shown that interfering with estrogen’s ability to stimulate the growth of breast cancer cells that have these receptors (ER-positive breast cancer cells) is an effective treatment approach.

Several drugs that interfere with estrogen binding to the ER have been approved by the FDA for the treatment of ER-positive breast cancer. Drugs called selective estrogen receptor modulators (SERMs), including tamoxifen ¹ and toremifene (Fareston®) ², bind to the ER and prevent estrogen binding. Another drug, fulvestrant (Faslodex®) ³, binds to the ER and promotes its destruction, thereby reducing ER levels inside cells.

Another class of targeted drugs that interfere with estrogen’s ability to promote the growth of ER-positive breast cancers is called aromatase inhibitors (AIs). The enzyme aromatase is necessary to produce estrogen in the body. Blocking the activity of aromatase lowers estrogen levels and inhibits the growth of cancers that need estrogen to grow. AIs are used mostly in women who have reached menopause because the ovaries of premenopausal women can produce enough aromatase to override the inhibition. Three AIs have been approved by the FDA for the treatment of ER-positive breast cancer: Anastrozole (Arimidex®) ⁴, exemestane (Aromasin®) ⁵, and letrozole (Femara®) ⁶.

5. What are some other targeted therapies?

Targeted cancer therapies have been developed that interfere with a variety of other cellular processes. FDA-approved targeted therapies are listed below:

• Some targeted therapies block specific enzymes and growth factor receptors involved in cancer cell proliferation. These drugs are also called signal transduction inhibitors.

• Imatinib mesylate (Gleevec®) ⁷ is approved by the FDA to treat gastrointestinal stromal tumor (a rare cancer of the gastrointestinal tract) and certain kinds of leukemia. It targets several members of a class of proteins called tyrosine kinase enzymes that participate in signal transduction. These enzymes are overactive in some cancers, leading to uncontrolled growth. It is a small-molecule drug, which means that it can pass through cell membranes and reach targets inside the cell.
• Dasatinib (Sprycel®) ⁸ is FDA approved to treat some patients with chronic myeloid leukemia and acute lymphoblastic leukemia. It is a small-molecule inhibitor of several tyrosine kinase enzymes.
• Nilotinib (Tasigna®) ⁹ is FDA approved to treat some patients with CML. It is another small-molecule tyrosine kinase inhibitor.
• Trastuzumab (Herceptin®) ¹⁰ is FDA approved for the treatment of certain types of breast cancer. It is a monoclonal antibody that binds to the human epidermal growth factor receptor 2 (HER-2). HER-2, a receptor with tyrosine kinase activity, is expressed at high levels in some breast cancers and also some other types of cancer. The mechanism by which trastuzumab acts is not completely understood, but one likely possibility is that by binding to HER-2 on the surface of tumor cells that express high levels of HER-2, it prevents HER-2 from sending growth-promoting signals. Trastuzumab may have other effects as well, such as inducing the immune system to attack cells that express high levels of HER-2.
• Gefitinib (Iressa®) ¹¹ is approved by the FDA to treat patients with advanced
  non-small cell lung cancer. Its use is restricted to patients who, in the opinion of their treating physician, are currently benefiting, or have previously benefited, from gefitinib treatment. This small-molecule drug inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), which is overproduced by many types of cancer cells.
  
• Erlotinib (Tarceva®) ¹² is approved by the FDA to treat metastatic non-small cell lung cancer and pancreatic cancer that cannot be removed by surgery or has metastasized. This small-molecule drug inhibits the tyrosine kinase activity of EGFR.
• Cetuximab (Erbitux®) ¹³ is a monoclonal antibody that is FDA approved for treating some patients with squamous cell carcinoma of the head and neck or colorectal cancer. It binds to the external portion of EGFR, thereby preventing the receptor from being activated by growth signals, which may inhibit signal transduction and lead to antiproliferative effects.
• Lapatinib (Tykerb®) ¹⁴ is FDA approved for the treatment of certain types of advanced or metastatic breast cancer. This small-molecule drug inhibits several tyrosine kinases, including the tyrosine kinase activity of HER-2. Lapatinib treatment prevents HER-2 signals from activating cell growth.
• Panitumumab (Vectibix®) ¹⁵ is FDA approved to treat some patients with metastatic colon cancer. This monoclonal antibody attaches to EGFR and prevents it from sending growth signals.
• Temsirolimus (Torisel®) ¹⁶ is approved to treat patients with advanced renal cell carcinoma. This small-molecule drug is a specific inhibitor of a kinase called mTOR that is activated in tumor cells and stimulates their growth and proliferation.

• Some targeted therapies induce cancer cells to undergo apoptosis (cell death).

• Bortezomib (Velcade®) ¹⁷ is approved by the FDA to treat some patients with multiple myeloma. It is also approved for the treatment of some patients with mantle cell lymphoma. Bortezomib causes cancer cells to die by interfering with the action of a large cellular structure called the proteasome, which degrades proteins. Proteasomes control the degradation of many proteins that regulate cell proliferation. By blocking this process, bortezomib causes cancer cells to die. Normal cells are affected, too, but to a lesser extent.

• Other targeted therapies block the growth of blood vessels to tumors (angiogenesis). To grow beyond a certain size, tumors must obtain a blood supply to get the oxygen and nutrients needed for continued growth. Treatments that interfere with angiogenesis may block tumor growth.

• Bevacizumab (Avastin®) ¹⁸ is a monoclonal antibody that is approved for the treatment of glioblastoma. It is also approved for some patients with non-small cell lung cancer, metastatic breast cancer, and metastatic colorectal cancer. Bevacizumab binds to the vascular endothelial growth factor (VEGF). This prevents VEGF from interacting with its receptors on endothelial cells, a step that is necessary for the initiation of new blood vessel growth.
  
• Sorafenib (Nexavar®) ¹⁹ is a small-molecule inhibitor of tyrosine kinases that is FDA approved for the treatment of advanced renal cell carcinoma and some cases of hepatocellular carcinoma. One of the kinases that sorafenib inhibits is involved in the signaling pathway that is initiated when VEGF binds to its receptors. As a result, new blood vessel development is halted. Sorafenib also blocks an enzyme that is involved in cell growth and division.
  
• Sunitinib (Sutent®) ²⁰ is another small-molecule tyrosine kinase inhibitor that is FDA approved for the treatment of patients with metastatic renal cell carcinoma or gastrointestinal stromal tumor that is not responding to imatinib. It blocks kinases involved in VEGF signaling, thereby inhibiting angiogenesis and cell proliferation.

• Some targeted therapies act by helping the immune system to destroy cancer cells.
  

• Rituximab (Rituxan®) ²¹ is a monoclonal antibody that is approved to treat certain types of B-cell non-Hodgkin lymphoma. It recognizes a molecule called CD20 that is found on B cells. When rituximab binds to these cells, it triggers an immune response that results in their destruction. Rituximab may also induce apoptosis.
  
• Alemtuzumab (Campath®) ²² is approved to treat patients with B-cell chronic lymphocytic leukemia. It is a monoclonal antibody that is directed against CD52, a protein found on the surface of normal and malignant B and T cells and many other cells of the immune system. Binding of alemtuzumab to CD52 triggers an immune response that destroys the cells.

• Another class of targeted therapies includes monoclonal antibodies that deliver toxic molecules to cancer cells specifically.

• Gemtuzumab ozogamicin (Mylotarg®) ²³ is FDA approved to treat some patients with acute myeloid leukemia. It is a monoclonal antibody directed against the protein CD33, which is found on the surface of leukemic blast cells, linked to an antitumor substance called calicheamicin. Gemtuzumab ozogamicin is taken up by cells that express CD33 and, once inside, the calicheamicin portion prevents DNA synthesis.
  
• Tositumomab and 131I-tositumomab (Bexxar®) ²⁴ is approved to treat certain types of B-cell non-Hodgkin lymphoma. It is a mixture of monoclonal antibodies that recognize the CD20 molecule. Some of the antibodies in the mixture are linked to a radioactive substance called iodine-131. The 131I-tositumomab component delivers radioactive energy to CD20-expressing B cells specifically, reducing collateral damage to normal cells of the type that is seen with traditional radiotherapy. In addition, the binding of tositumomab to the CD20-expressing B cells triggers the immune system to destroy these cells.
  
• Ibritumomab tiuxetan (Zevalin®) ²⁵ is FDA approved to treat some patients with B-cell non-Hodgkin lymphoma. It is a monoclonal antibody directed against CD20 that is linked to a molecule that can bind radioisotopes such as indium-111 or yttrium-90. The radiolabeled forms of Zevalin deliver a high dose of radioactivity to cells that express CD20.
  

• Cancer vaccines and gene therapy are often considered to be targeted therapies because they interfere with the growth of specific cancer cells. Information about these treatments can be found in the following National Cancer Institute (NCI) fact sheets, which are available on the Internet or by calling NCI’s Cancer Information Service (CIS) (see below):

—Biological Therapies for Cancer includes information about monoclonal antibodies and cancer vaccines. This fact sheet is available at http://www.cancer.gov/cancertopics/factsheet/Therapy/biological on the Internet.


—Cancer Vaccines contains information on vaccines intended to treat cancer, as well as those intended to prevent it. This fact sheet is available at http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines on the Internet.


—Gene Therapy for Cancer discusses research with genetic material in developing cancer therapies, including risks, benefits, and ethical issues. This fact sheet can be found at http://www.cancer.gov/cancertopics/factsheet/Therapy/gene on the Internet.

6. What impact will targeted therapies have on cancer treatment?

Targeted cancer therapies give doctors a better way to tailor cancer treatment, especially when a target is present in some but not all tumors of a particular type, as is the case for HER-2. Eventually, treatments may be individualized based on the unique set of molecular targets produced by the patient’s tumor. Targeted cancer therapies also hold the promise of being more selective for cancer cells than normal cells, thus harming fewer normal cells, reducing side effects, and improving quality of life.

Nevertheless, targeted therapies have some limitations. Chief among these is the potential for cells to develop resistance to them. In some patients who have developed resistance to imatinib, for example, a mutation in the BCR-ABL gene has arisen that changes the shape of the protein so that it no longer binds this drug as well. In most cases, another targeted therapy that could overcome this resistance is not available. It is for this reason that targeted therapies may work best in combination, either with other targeted therapies or with more traditional therapies.

7. Where can I find information about clinical trials of targeted therapies?

FDA-approved targeted cancer therapies continue to be studied in clinical trials, as indicated by the list below. In the HTML version of this fact sheet on NCI’s Web site (http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted), the drug names are links to search results for trials in NCI’s clinical trials database. This database can also be searched on NCI’s Web site by visiting http://www.cancer.gov/clinicaltrials/search on the Internet. The database includes all NCI-funded clinical trials and many other studies conducted by investigators at hospitals and medical centers in the United States and other countries around the world.

Targeted Cancer Therapies Currently Being Studied in Clinical Trials:
Alemtuzumab (Campath®) ²⁶
Anastrozole (Arimidex®) ²⁷
Bevacizumab (Avastin®) ²⁸
Bortezomib (Velcade®) ²⁹
Cetuximab (Erbitux®) ³⁰
Dasatinib (Sprycel®) ³¹
Erlotinib Hydrochloride (Tarceva®) ³²
Exemestane (Aromasin®) ³³
Fulvestrant (Faslodex®) ³⁴
Gefitinib (Iressa®) ³⁵
Gemtuzumab Ozogamicin (Mylotarg®) ³⁶
Ibritumomab Tiuxetan (Zevalin®) ³⁷
Imatinib Mesylate (Gleevec®) ³⁸
Lapatinib Ditosylate (Tykerb®) ³⁹
Letrozole (Femara®) ⁴⁰
Nilotinib (Tasigna®) ⁴¹
Panitumumab (Vectibix®) ⁴²
Rituximab (Rituxan®) ⁴³
Sorafenib Tosylate (Nexavar®) ⁴⁴
Sunitinib Malate (Sutent®) ⁴⁵
Tamoxifen ⁴⁶
Temsirolimus (Torisel®) ⁴⁷
Toremifene (Fareston®) ⁴⁸
Tositumomab and 131I-tositumomab (Bexxar®) ⁴⁹
Trastuzumab (Herceptin®) ⁵⁰

8. What are some resources for more information?

NCI’s Molecular Targets Development Program (MTDP) is working to identify and evaluate molecular targets that may be candidates for drug development. As part of NCI’s Center for Cancer Research (CCR), the MTDP provides research support for NCI-designated, high-priority drug discovery, development, and research focused on specific molecular targets, pathways, or processes. The MTDP’s Web site is located at http://home.ncifcrf.gov/mtdp/ on the Internet.

NCI’s Chemical Biology Consortium (CBC) will focus efforts and resources on drug candidate identification and optimization to enhance the entry of early-stage drug candidates into the NCI therapeutics pipeline. The CBC is part of the NCI’s Experimental Therapeutics Program, which is a collaborative effort of CCR and NCI’s Division of Cancer Treatment and Diagnosis. More information about the CBC, which is being launched in August 2009, can be found at http://dctd.cancer.gov/CurrentResearch/ChemicalBioConsortium.htm on the Internet.

# # #

• National Cancer Institute Fact Sheet 2.11, Clinical Trials ⁵¹
  (http://www.cancer.gov/cancertopics/factsheet/Information/clinical-trials)
• National Cancer Institute Fact Sheet 7.2, Biological Therapies for Cancer ⁵²
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/biological)
• National Cancer Institute Fact Sheet 7.18, Gene Therapy for Cancer ⁵³
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/gene)
• National Cancer Institute Fact Sheet 7.42, Angiogenesis Inhibitors Therapy ⁵⁴
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors)
• National Cancer Institute Fact Sheet 7.45, Herceptin® (Trastuzumab) ⁵⁵
  (http://www.cancer.gov/cancertopics/factsheet/therapy/herceptin)
• National Cancer Institute Fact Sheet 7.56, Cancer Vaccines ⁵⁶
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines)
• Understanding Cancer Series: Targeted Therapies Tutorial ⁵⁷
  (http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies)
• What You Need To Know About™ Cancer—An Overview ⁵⁸
  (http://www.cancer.gov/cancertopics/wyntk/overview)

How can we help?

We offer comprehensive research-based information for patients and their families, health professionals, cancer researchers, advocates, and the public.

• Call NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237)
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Glossary Terms

An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called acute lymphocytic leukemia and ALL.

An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute nonlymphocytic leukemia, AML, and ANLL.

A type of monoclonal antibody used in the treatment of leukemia. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. Also called Campath-1H.

Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels that tumors need to grow. This is caused by the release of chemicals by the tumor.

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

Having to do with stopping abnormal cell growth.

A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.

A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer.

A type of immune cell that makes proteins called antibodies, which bind to microorganisms and other foreign substances, and help fight infections. A B cell is a type of white blood cell. Also called B lymphocyte.

A gene formed when pieces of chromosomes 9 and 22 break off and trade places. The ABL gene from chromosome 9 joins to the BCR gene on chromosome 22, to form the BCR-ABL fusion gene. The changed chromosome 22 with the fusion gene on it is called the Philadelphia chromosome. The BCR-ABL fusion gene is found in most patients with chronic myelogenous leukemia (CML), and in some patients with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML).

A drug used to treat several types of cancer, including certain types of colorectal, lung, breast, and kidney cancers and glioblastoma. It is also being studied in the treatment of other types of cancer. Bevacizumab binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called Avastin.

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in biological therapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biotherapy, BRM therapy, and immunotherapy.

An immature blood cell.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.

A drug used to treat multiple myeloma. It is also used to treat mantle cell lymphoma in patients who have already received at least one other type of treatment and is being studied in the treatment of other types of cancer. Bortezomib blocks several molecular pathways in a cell and may cause cancer cells to die. It is a type of proteasome inhibitor and a type of dipeptidyl boronic acid. Also called PS-341 and velcade.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

The Cancer Information Service is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER (1-800-422-6237), or by using the LiveHelp instant-messaging service at https://cissecure.nci.nih.gov/livehelp/welcome.asp. Also called CIS.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

An increase in the number of cells as a result of cell growth and cell division.

Treatment with drugs that kill cancer cells.

Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.

An indolent (slow-growing) cancer in which too many immature lymphocytes (white blood cells) are found mostly in the blood and bone marrow. Sometimes, in later stages of the disease, cancer cells are found in the lymph nodes and the disease is called small lymphocytic lymphoma. Also called CLL.

A slowly progressing disease in which too many white blood cells (not lymphocytes) are made in the bone marrow. Also called chronic granulocytic leukemia, chronic myelogenous leukemia, and CML.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

In science, a substance that is made up of more than one ingredient.

The process of identifying a disease, such as cancer, from its signs and symptoms.

Widely spread; not localized or confined.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

The amount of medicine taken, or radiation given, at one time.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also called epidermal growth factor receptor, ErbB1, and HER1.

The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart.

A protein that speeds up chemical reactions in the body.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

A protein found inside the cells of the female reproductive tissue, some other types of tissue, and some cancer cells. The hormone estrogen will bind to the receptors inside the cells and may cause the cells to grow. Also called ER.

Having to do with beliefs about what is right and wrong in terms of how people behave. Also called moral.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered experimental in other diseases or conditions. Also called investigational.

Refers to the stomach and intestines. Also called GI.

A type of tumor that usually begins in cells in the wall of the gastrointestinal tract. It can be benign or malignant. Also called GIST.

A drug that is used to treat certain types of non-small cell lung cancer and is being studied in the treatment of other types of cancer. It is a type of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Also called Iressa and ZD1839.

A monoclonal antibody combined with a toxic substance that is used to treat certain types of acute myeloid leukemia in older patients and is being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Gemtuzumab ozogamicin is a type of antibody-drug conjugate. Also called gemtuzumab and Mylotarg.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Treatment that alters a gene. In studies of gene therapy for cancer, researchers are trying to improve the body's natural ability to fight the disease or to make the cancer cells more sensitive to other kinds of therapy.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma multiforme, and grade IV astrocytoma.

A substance made by the body that functions to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy.

A type of adenocarcinoma, the most common type of liver tumor.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

A protein involved in normal cell growth. It is found on some types of cancer cells, including breast and ovarian. Cancer cells removed from the body may be tested for the presence of human epidermal growth factor receptor 2 to help decide the best type of treatment. Human epidermal growth factor receptor 2 is a type of receptor tyrosine kinase. Also called c-erbB-2, HER2/neu, and human EGF receptor 2.

A drug used to treat different types of leukemia and other cancers of the blood, gastrointestinal stromal tumors, skin tumors called dermatofibrosarcoma protuberans, and a rare condition called systemic mastocytosis. It is also being studied in the treatment of other types of cancer. Imatinib mesylate blocks the protein made by the bcr/abl oncogene. It is a type of tyrosine kinase inhibitor. Also called Gleevec and STI571.

The activity of the immune system against foreign substances (antigens).

The complex group of organs and cells that defends the body against infections and other diseases.

An element that is necessary for the body to make thyroid hormone. It is found in shellfish and iodized salt.

A type of enzyme that causes other molecules in the cell to become active. Some kinases work by adding chemicals called phosphates to other molecules, such as sugars or proteins. Kinases are a part of many cell processes. Some cancer treatments target certain kinases that are linked to cancer.

A medical procedure that involves testing a sample of blood, urine, or other substance from the body. Tests can help determine a diagnosis, plan treatment, check to see if treatment is working, or monitor the disease over time.

A drug used with another anticancer drug to treat breast cancer that is HER2 positive and has advanced or metastasized (spread to other parts of the body) after treatment with other drugs. Lapatinib is also being studied in the treatment of other types of cancer. It is a type of ErbB-2 and EGFR dual tyrosine kinase inhibitor. Also called GW572016, lapatinib ditosylate, and Tykerb.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

An aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma that usually occurs in middle-aged or older adults. It is marked by small- to medium-size cancer cells that may be in the lymph nodes, spleen, bone marrow, blood, and gastrointestinal system.

A very thin layer of tissue that covers a surface.

The time of life when a woman’s ovaries stop producing hormones and menstrual periods stop. Natural menopause usually occurs around age 50. A woman is said to be in menopause when she hasn’t had a period for 12 months in a row. Symptoms of menopause include hot flashes, mood swings, night sweats, vaginal dryness, trouble concentrating, and infertility.

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

A type of cancer that begins in plasma cells (white blood cells that produce antibodies). Also called Kahler disease, myelomatosis, and plasma cell myeloma.

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

Cancer that arises in plasma cells, a type of white blood cell.

Any of a large group of cancers of lymphocytes (white blood cells). Non-Hodgkin lymphomas can occur at any age and are often marked by lymph nodes that are larger than normal, fever, and weight loss. There are many different types of non-Hodgkin lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow-growing) types, and they can be formed from either B-cells or T-cells. B-cell non-Hodgkin lymphomas include Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma. T-cell non-Hodgkin lymphomas include mycosis fungoides, anaplastic large cell lymphoma, and precursor T-lymphoblastic lymphoma. Lymphomas that occur after bone marrow or stem cell transplantation are usually B-cell non-Hodgkin lymphomas. Prognosis and treatment depend on the stage and type of disease. Also called NHL.

A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.

A chemical compound (such as protein, fat, carbohydrate, vitamin, or mineral) contained in foods. These compounds are used by the body to function and grow.

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

A colorless, odorless gas. It is needed for animal and plant life. Oxygen that is breathed in enters the blood from the lungs and travels to the tissues.

A disease in which malignant (cancer) cells are found in the tissues of the pancreas. Also called exocrine cancer.

Medical doctor.

The outer membrane of a cell.

Having to do with the time before menopause. Menopause ("change of life") is the time of life when a woman's menstrual periods stop permanently.

In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

Giving off radiation.

An unstable form of a chemical element that releases radiation as it breaks down and becomes more stable. Radioisotopes may occur in nature or be made in a laboratory. In medicine, they are used in imaging tests and in treatment. Also called radionuclide.

Any compound that has been joined with a radioactive substance.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.

A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell.

The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.

A monoclonal antibody used to treat certain types of B-cell non-Hodgkin lymphoma and symptoms of rheumatoid arthritis. Monoclonal antibodies are made in the laboratory and can bind to substances in the body, including cancer cells. Rituximab binds to the protein called CD20, which is found on B-cells, and may kill cancer cells. Also called Rituxan.

A person who has studied science, especially one who is active in a particular field of investigation.

A drug that acts like estrogen on some tissues but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. Also called selective estrogen receptor modulator.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

The process by which a cell responds to substances in its environment. The binding of a substance to a molecule on the surface of a cell causes signals to be passed from one molecule to another inside the cell. These signals can affect many functions of the cell, including cell division and cell death. Cells that have permanent changes in signal transduction molecules may develop into cancer.

Describes a group of molecules in a cell that work together to control one or more cell functions, such as cell division or cell death. After the first molecule in a pathway receives a signal, it activates another molecule. This process is repeated until the last molecule is activated and the cell function involved is carried out. Abnormal activation of signaling pathways can lead to cancer, and drugs are being developed to block these pathways. This may help block cancer cell growth and kill cancer cells.

A drug used to treat advanced kidney cancer and a type of liver cancer that cannot be removed by surgery. It is also being studied in the treatment of other types of cancer. Sorafenib stops cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of kinase inhibitor and a type of antiangiogenesis agent. Also called BAY 43-9006, Nexavar, and sorafenib tosylate.

An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

A type of immune cell that can attack foreign cells, cancer cells, and cells infected with a virus. T cells can also help control immune responses. A T cell is a type of white blood cell. Also called T lymphocyte and thymocyte.

A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treatments.

Treatment.

A monoclonal antibody that is used in the treatment of certain types of non-Hodgkin lymphoma. When tositumomab and iodine I 131 tositumomab (a form of tositumomab that has been chemically changed by adding radioactive iodine) are given together, the combination is called the Bexxar regimen. Also called Bexxar regimen, iodine I 131 tositumomab, and tositumomab and iodine I 131 tositumomab.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

A monoclonal antibody that binds to HER2 (human epidermal growth factor receptor 2), and can kill HER2-positive cancer cells. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Trastuzumab is used to treat breast cancer that is HER2-positive and has spread after treatment with other drugs. It is also used with other anticancer drugs to treat HER2-positive breast cancer after surgery. Trastuzumab is also being studied in the treatment of other types of cancer. Also called Herceptin.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A drug that interferes with cell communication and growth and may prevent tumor growth. Some tyrosine kinase inhibitors are used to treat cancer.

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

A substance made by cells that stimulates new blood vessel formation. Also called vascular endothelial growth factor.

A metal of the rare earth group of elements. A radioactive form of yttrium may be attached to a monoclonal antibody or other molecule that can locate and bind to cancer cells and be used to diagnose or treat some types of cancer.

A monoclonal antibody that is used to treat certain types of B-cell non-Hodgkin lymphoma and is being studied in the treatment and detection of other types of B-cell tumors. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Ibritumomab binds to the protein called CD20, which is found on B cells. It is linked to the compound tiuxetan. This allows certain radioisotopes to be attached before it is given to a patient. It is a type of monoclonal antibody-chelator conjugate. Also called ibritumomab tiuxetan.