The conventional therapies used to treat cancers that we are all familiar with such as radiation, chemotherapy, and surgery, have served us well in our battle against the disease. But they are not without significant side effects. Healthy surrounding tissues, and even parts of our bodies remote from the area of the cancer can be affected by these treatments. Ideally science would like to find methods of treatment that are more specific to killing just the cancer cells and not affecting healthy tissues at the same time. As we learn more about the mechanisms by which our cells operate, the means by which they replicate, become malignant, or even just their methods of obtaining the nutrients that allow them to survive, we are finding that using these paths of normal cellular activity, we may be able to stop the growth of, or even kill, very specific cells such as those that have become cancerous. This is what targeted therapies endeavor to accomplish. These very specific methods which interfere with some aspect of cellular life without harming healthy cells in the process are referred to as targeted therapies. They interfere with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. Because these biological molecules are called “molecular targets,” these therapies are sometimes called “molecular-targeted drugs,” “molecularly targeted therapies,” “targeted drug therapy”, or other similar names. By altering molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current treatments and less harmful to normal cells. Their use is relatively new, and new discoveries are emerging at a rapid pace.
Cellular changes that lead to cancer
In order to understand how targeted and biologic therapies work, a very basic understanding of the cancer process is necessary. Cells grow and divide to form new cells as the body needs them. As cells grow old, they die, and new cells take their place. This process of normal, programmed cell death and replacement is called apoptosis. Occasionally, this orderly process goes wrong. Cells form when the body does not need them, and old cells do not die when they should. Extra cells can form a mass of tissue (a group or layer of cells that work together to perform a similar function) called a growth or tumor. Cells in cancerous tumors are not normal and divide uncontrollably, invading and damaging nearby tissues and organs. In addition, cancer cells can metastasize or break away from a malignant tumor and spread to other parts of the body. Under normal conditions, cell growth and division are mainly under the control of an arrangement of chemical and molecular signals that give instructions to cells. Changes or genetic alterations can disrupt the signaling process so that cells no longer grow and divide in a normal fashion, or no longer die when they are supposed to. Contributing to the cancer process are alterations in two types of genes. Proto-oncogenes are normal genes that are involved in cell growth and division. Changes, or mutations in these genes lead to the development of oncogenes which can promote or allow excessive and continuous cell growth and division. Tumor suppressor genes are normal genes that slow down cell growth and division. When a tumor suppressor gene does not work properly, cells may be unable to stop growing and dividing, leading to tumor growth.
Genetic changes that are not corrected by the cell can also lead to the production of abnormal proteins. Normally, proteins interact with each other as a kind of relay team to carry out the work of the cell. For example, when molecules called growth factors (GFs) attach themselves to corresponding growth factor receptors (GFRs) on the surface of the cell, a process carried out by proteins signals the cell to divide. Damaged proteins may not respond to these normal signals, over-respond to normal signals, or otherwise fail to carry out their normal functions. When these failures or errors occur, cancer develops causing it to reproduce excessively and allowing that cell to live longer than normal cells. As cancer cells continue to reproduce, their daughter cells also contain the cancer as well.
The immune system and its components
The immune system is a complex network of cells and organs that work together to defend the body against attacks by “foreign” or “non-self” invaders. This network is one of the body’s main defenses against infection and disease. The immune system works against diseases, including cancer, in a variety of ways. For example, the immune system may recognize the difference between healthy cells and abnormal cells (including cancer cells) in the body and works to eliminate these cells. However, the immune system does not always recognize cancer cells as foreign or abnormal. Also, cancer may develop when the immune system breaks down or does not function adequately. As we age there is a normal decline in the effectiveness of our immune systems, and they become increasingly incompetent with age. Biological therapies are designed to repair, stimulate, or enhance the immune system’s responses. (More about the immune system…)
Mechanisms of targeted cancer therapies
Targeted cancer therapies interfere with cancer cell growth and division in different ways and at various points during the development, growth, and spread of cancer. Many of these therapies focus on proteins that are involved in the signaling process. By blocking the signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can help to stop the growth and division of cancer cells.
Targeted cancer therapies include several types of drugs. Some examples are listed below, but many novel new drugs are currently in clinical trials and may be introduced in the near future. “Small-molecule” drugs block specific enzymes and GFRs involved in cancer cell growth. These drugs are also called signal-transduction inhibitors. Think of a small receptor site on the outside of a cell, that is designed to have a signal protein attach to it, which when attached, signals the cell to duplicate. If a drug is able to block that receptor site on the surface of a cancerous cell, when the signal protein comes to tell it to replicate it will not be able to deliver the message. This effectively stops that cancer cell from duplicating into additional