Gefitinib is a new drug used in the treatment of certain types of cancer. Acting in a similar manner to imatinib, gefitinib selectively targets the mutant proteins in malignant cells. It is marketed by AstraZeneca under the trade name Iressa®. The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1. ... Half-Life is a science fiction first-person shooter computer game developed by Valve Software and published by Sierra Entertainment in 1998, based on a heavily-modified Quake game engine. ... --212. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... A drug is any substance that can be used to modify a chemical process or processes in the body, for example to treat an illness, relieve a symptom, enhance a performance or ability, or to alter states of mind. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Imatinib is a drug used to treat certain types of cancer. ... AstraZeneca PLC, is a large Anglo-Swedish pharmaceutical company formed on 6 April 1999 by the merger of Swedish Astra AB and British Zeneca Group PLC. Zeneca was part of Imperial Chemical Industries prior to a demerger in 1993. ...

Mechanism of action

Gefitinib is the first selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. The target protein (tyrosine kinase) is also sometimes referred to as Her1 or ErbB-1 depending on the literature source. GOD DAMN IT WHY DOES IT KEEP SAYINBG I HAVE PRIVATE MESSAGES!!! I DIDNnT DO ANY FUCKING THING!!!!!!!!!!!!!!!!!!!!!!!!!!!!! ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ...

EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. This leads to inappropriate activation of the apoptotic Ras signal transduction cascade, eventually leading to uncontrolled cell proliferation. Research on Gefitinib-sensitive non-small cell lung cancers has shown that a mutation in the EGFR tyrosine kinase domain is responsible for activating anti-apoptotic pathways. (Pao et al. 2004, Sordella et al. 2004) In medicine, carcinoma is any cancer that arises from epithelial cells. ... In biology, apoptosis (from the Greek words apo = from and ptosis = falling, pronounced ap-a-tow-sis[1]) is one of the main types of programmed cell death (PCD). ... RAS is an acronym that could mean one of the following: Redundant Acronym Syndrome Remote Access Service Request-A-Song. ... In biology, signal transduction is any process by which a cell converts one kind of signal or stimulus into another. ...

Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Adenosine triphosphate (ATP) is the nucleotide known in biochemistry as the molecular currency of intracellular energy transfer; that is, ATP is able to store and transport chemical energy within cells. ...

Clinical uses

Gefitinib is currently only indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who have previously received chemotherapy. Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ... The incidence of lung cancer is highly correlated with smoking. ...

Whilst gefitinib has yet to be proven to be effective in other cancers, there is certainly potential for its use in the treatment of other cancers where EGFR overexpression is involved.

In 2004, AstraZeneca informed the United States Food and Drug Administration (FDA) that a large randomized study [1] failed to demonstrate a survival advantage for gefitinib in the treatment of non-small cell lung cancer (NSCLC). Whether progression-free survival is prolonged is not clear from this statement. AstraZeneca also withdrew their application to market gefitinib in Europe shortly after this announcement.

Genzyme Test

On September 26 2005, Genzyme Corp. announced that it will market a test to detect EGFR expression, designed to help predict which lung cancer patients may respond best to some therapies, including gefitinib and erotinib. This method is to be used identify ahead of time which patient may be helped. September 26 is the 269th day of the year (270th in leap years) in the Gregorian Calendar, with 96 days remaining. ...

The test, expected to cost about $975, examines the genetics of tumors removed for biopsy for mutations that make them susceptible to treatment.

The EGFR expression test may also help Genentech and AstraZeneca win regulatory approval for use of their drugs as initial therapies. Currently, the TK inhibitors are approved for use only after other drugs fail. In the case of gefitinib, the drug works only in about 10% of patients with advanced non-small-cell lung cancer, the most common type of lung cancer. This led the Food and Drug Administration this summer to partially withdraw the drug in the U.S., no longer allowing its prescription for new patients. The drug remains on the market in Europe.

Adverse effects

As gefitinib is a selective chemotherapeutic agent, its tolerability profile is far superior to previous cytotoxic agents. Adverse drug reactions (ADRs) do still occur, however, but are preferable to the fatal consequences of not taking the therapy. Cytotoxicity is the quality of being poisonous to cells. ...

Common

Acne is reported very commonly. Other common side-effects include: diarrhoea, nausea, vomiting, anorexia, stomatitis, dehydration, skin reactions, paronychia, asymptomatic elevations of liver enzymes, asthenia, conjunctivitis, blepharitis. (Rossi, 2004) Diarrhoea is the correct way to spell the word Diarrhoea. ... Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... Anorexia (deriving from the Greek όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... Stomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, and roof or floor of the mouth. ... Dehydration is the removal of water (hydor in ancient Greek) from an object. ... Paronychia is an often tender infection or inflammation around the base of the nail fold. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ... Asthenia is a medical term denoting weakness, lack of energy and strength. ... Blepharitis is a medical condition relating to the inflammation of eyelids and eyelashes. ...

Infreqent

These include: interstitial lung disease, corneal erosion, aberrant eyelash and hair growth. (Rossi, 2004)

References

• Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
• Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306-11. Fulltext. PMID 15329413.
• Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004;305:1163-7. PMID 15284455.
• Genzyme "Genzyme Launches Exclusive Lung Cancer Test" Press Release September 27, 2005

The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly general practitioners and pharmacists) in Australia. ... The Proceedings of the National Academy of Sciences (USA), mostly commonly referred to as PNAS, is the official publication of the National Academy of Sciences of the United States of America. ...

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