An Overview of Tyrosine Kinase Inhibitors

Tyrosine Kinase inhibitors are a class of chemotherapy drugs. Drugs in this classification include: Axitinib, Bosutinib, Cediranib, Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Lestaurtinib, Nilotinib, Semaxanib, Sunitinib, and Vandetanib. These drugs are prescribed by themselves or often in a treatment package (combination therapy) which includes Tyrosine Kinase inhibitors along with other methods of treating cancer.

These inhibitors are commonly used in the treatment of cancers including: non-small-cell lung cancer (NSCLC), head and neck, colorectal, renal, prostate, breast, and primary brain cancer. They are finding increasing use in the treatment of mesothelioma. This drug type has only been around since the 1980's, so some drugs are currently still in clinical trials while others are in current use.

Tyrosine Kinase is an enzyme which transports phosphates from ATP to a protein's tyrosine residue. Therefore, a Tyrosene Kinase inhibitor prevents the phosphate groups from being transferred. Research indicates that mutations which make Tyrosene Kinases constantly active can be a contributing factor in the development of cancerous cells. So, when an inhibitor is used, the cell communication and reproduction is reduced, and cancerous cell growth will be reduced to the point of stopping tumor growth. It operates by promoting apoptosis, which is a form of programmed and selective cell destruction, and by discouraging angiogenesis, the formation and growth of new blood vessels that need to connect to old blood vessels to nourish tissue. Through destroying the cancerous cells and preventing a blood supply from being formed, tumors will halt their growth and possibly reduce in size.

These inhibitors are targeted therapies which are intended to have specific effects on cancerous cells as opposed to a mass effect on an area of tissue. One of the most pronounced effects of Tyrosene Kinase inhibitors are their ability to stunt the epidermal growth factor receptor (EGFR). Epidermal growth factor receptors are found on the surface of cells, and they affect the regulation of cell growth and development. Certain viruses carry genetic information which mutates the epidermal growth factor receptor, and when it is modified, a signal is sent to overproduce cells in that region. For breast cancer, study results have shown a link between the reduction of EGFR and the oestrogen receptor (ER) in pre-clinical studies, so the effects of faulty epidermal growth factor receptors can have far-reaching effects on other factors considered to contribute to the development of cancer. For example, erbB receptors are Type 1 transmembrane receptors which are found in large amounts inside of tumors. The excessive activation of signals in these receptors can be a contributing factor in the development of breast cancer as well as others as it causes the uncontrolled growth of cells.

Epidermal growth factor receptors have been researched since the early 1980s. It was discovered that some carcinogenic viruses, namely erythroblastosis tumour viruses, alter the operation of human epidermal growth factor receptor. The presence of those receptors in large quantities in several tumors suggests that they are a significant factor of carcinogenesis, the formation of cancerous cells. Since the 1980's, many studies have been conducted to study the role of epidermal growth factor receptors in cancer development, and researchers have made attempts to selectively inhibit their signaling pathways.

One study used antibodies which block the extracellular, or parts outside of the cell, portion of the receptor to prevent signaling. Another attempt created low-molecular-weight substances referred to as cell signaling inhibitors which block the receptors from inside the cell.

The first targeted Tyrosine Kinase inhibitor developed and released to the market is Imatinib. It was developed in the late 1990's by Novartis, and the brand-name Gleevec was approved by the FDA in May of 2001. TIME magazine referred to Gleevec as a magic bullet to cure cancer in an article published in the same month. The cost of Gleevec, which is around thirty-two thousand dollars a year for a 400mg per-day-dose, can be prohibitive for many people. However, others cited it as the justification for the high cost of prescription drugs as it works much better than the preceding treatments without destroying the healthy tissue in a patient.

Research is currently being conducted into Tyrosene Kinase inhibitors to refine the old drugs and develop new ones to target cancerous cells more specifically and destroy them. Several clinical trials for a variety of drugs are currently underway to test current theories and drugs for their effectiveness across a gamut of cancers, and while the results appear to be promising for quite a few cases, current drugs are not fully capable of treating most patients with solid tumors, so more research must be conducted to develop the drugs.

Lapatinib is a relatively new drug which was approved by the FDA on March 13th of 2007. It is an oral anti-cancer drug which is used to treat solid tumors for lung and breast cancer. It is used in conjunction with capecitabine, trade name Xeloda, for patients with advanced metastatic breast cancer. Often, it is used on patients who have undergone treatment with the intravenous drug trastuzumab, trade name Herceptin, and other anti-cancer drugs referred to as taxanes and anthracyclines. According to trials conducted on patients with HER2/neu positive metastatic breast cancer and have not shown improvement to other methods of treatment including: anthracycline, taxanes, and trastuzumab, the combination of lapatinib and capecitabine has been shown to delay the growth of cancerous cells to a greater degree than capecitabine alone.

With all of the advances in this new category of drugs, one can expect many promising results to emerge from the current clinical trials and future developments to come. With the various combinations of specific-target Tyrosene Kinase inhibitor drugs, several types of cancer can be reduced, retarded, or eliminated through concentrated chemotherapy regimens. With Tyrosene Kinase inhibitors, patients with cancer are given more options and better choices for managing the disease without disrupting their quality of life to the degree that previous treatments have.

The government's orphan drugs program was set up to develop medications for rare diseases like mesothelioma.