Tyrosine kinase inhibitors
Tyrosine kinase inhibitors make up a class of drugs that attach to and block the action of a group of proteins called tyrosine kinases. Tyrosine kinases cause a chemical reaction that helps to transmit signals from the outside to the inside of the cell. Often these signals regulate cell growth and division. Thus, excessive tyrosine kinase activity can lead to the out-of-control growth found in cancer. There are many tyrosine kinases, and each inhibitor is designed to block just one of them. As a result, a patient can be treated with the inhibitor that blocks only the tyrosine kinase that functions abnormally in his/her cancer. This allows all of the other tyrosine kinases to carry out their usual functions throughout the body, helping to minimize unwanted side effects.
Protein
Proteins are large molecules that carry out a wide variety of functions in a cell, including structure, motility, signaling, and catalysis (speeding up and controlling chemical reactions). Proteins are made from 20 building blocks called amino acids. The synthesis of a protein begins by forming a long chain of amino acids. The identity of each amino acid at every position in the chain is unique for each protein and is specified by the genetic code in the cell’s DNA. Once the amino acid chain is formed, it coils into a three-dimensional structure that is necessary for the protein’s function.
Epidermal growth factor receptor
The epidermal growth factor receptor (EGFR) is a protein that is found on the surface of cells. Its job is to transmit signals from the outside to the inside of the cells. The signals come in the form of smaller proteins, such as the epidermal growth factor, that attach to the EGFR on the outer surface of the cell. Following this attachment, a portion of the EGFR called the tyrosine kinase domain, causes a reaction to occur inside the cell. This reaction alters the functions of other proteins, leading to an increase in cell growth and division. Excessive activity of the EGFR can lead to the out-of-control growth seen in cancer.
Signals
In any plant or animal that is made up of more than one cell, communication between cells is extremely important. Often, this communication occurs in the form of chemical signals that are produced by one cell and carried to another one, either close by, or at some distance away. To receive these signals, cells have specialized proteins, called receptors, to which the signals attach. Each chemical signal has its own specialized receptor. Once the signal molecule attaches to its receptor, the receptor causes chemical reactions to occur inside of the cell. These reactions lead to alterations in the function of other proteins. Signaling molecules that tell the cell to grow and divide and/or their receptors frequently function abnormally in cancer.
Mutation
A mutation is an alteration of the chemical structure of DNA. Such an alteration in the region that carries the code for a protein can lead to the synthesis of an abnormal form of the protein. In most cases, mutations lead to loss of function of the protein, but increased activity can also occur. Cancer cells carry large numbers of mutations, many of which lead to abnormal protein function that results in out-of-control cell growth and division.
Tyrosine kinase
A tyrosine kinase is a protein, or a portion of a protein, that causes a chemical reaction that modifies other proteins. The name “kinase” refers to a protein that attaches a phosphate group (a cluster of a phosphorous atom and four oxygen atoms) to an amino acid of another protein. Tyrosine is one of the twenty amino acids that are the building blocks of proteins, so a tyrosine kinase attaches a phosphate group to a tyrosine amino acid of another protein. The phosphate group changes the activities of the protein to which it is attached, leading to alterations in one or more cellular functions. Many proteins that are involved in transmission of signals that control cell growth and division are tyrosine kinases or contain a tyrosine kinase domain.
DNA
DNA (deoxyribonucleic acid) is a very long molecule found in the nucleus of cells. It is made up of a chain of four subunits, adenine, guanine, cytosine, and thymine. The order of the subunits in the chain serves as a chemical code that tells the cell how to make all of the proteins necessary for life. There is a specific region of DNA that carries the code for each protein. This region is referred to as the gene for that protein.
Genetic code
This is the order of adenine, guanine, cytosine, and thymine subunits in DNA that specifies how the cell will make all of the proteins needed for life. For every protein, there is a corresponding region in DNA that carries the code for that protein.
Non-small cell lung cancer
Lung cancers have been divided into two main categories based on the appearance of the cancer cells and the approach to treatment. Small cell lung cancer, representing about 10 to 15% of all lung cancers, grows very rapidly and has often spread to other parts of the body at the time of diagnosis. Non-small cell lung cancer actually includes three forms of lung cancer, adenocarcinoma (40% of all lung cancer), squamous cell carcinoma (25 to 30% of all lung cancer), and large cell carcinoma (10 to 15% of all lung cancer). Although these are distinct types of cancer, they have traditionally been treated in the same way and have shared a similar prognosis; however, there are important differences. Squamous cell carcinoma usually starts in the center of the lungs and is strongly associated with smoking. Large cell cancers can start anywhere in the lungs and are the fastest growing of the three forms. Adenocarcinomas tend to start in the outer parts of the lung and are slower growing. Although usually associated with former smokers, adenocarcinoma is the form most commonly seen in non-smokers and women. A subtype of adenocarcinoma, called bronchoalveolar carcinoma carries a better outlook than other forms of lung cancer.
Gefitinib
A tyrosine kinase inhibitor that blocks the activity of the EGFR, trade name Iressa. (Link to our own article on gefitinib).
Erlotinib
A tyrosine kinase inhibitor that blocks the activity of the EGFR, trade name Tarceva. (Link to our own article on erlotinib).
Bronchoalveolar carcinoma
This is a subtype of adenocarcinoma, which is a subtype of non-small cell lung cancer. Brochoalveolar carcinomas tend to occur more frequently in women and never smokers, and they carry a better outlook than other forms of lung cancer.