THE BIOLOGICAL AND CLINICAL SIGNIFICANCE OF P-GLYCOPROTEIN IN CANCER

FACULTY OF SCIENCEMODULAR DEGREE SCHEME

BSc HONOURS DEGREEINPHARMACOLOGY

Kudakwashe Emmanuel MupamhangaK0433939The Biological and Clinical Significanceof P-Glycoprotein in cancer

THE BIOLOGICAL AND CLINICAL SIGNIFICANCE OF P-GLYCOPROTEIN IN CANCER

ABSTRACT & BACKGROUNDCANCER

–BIOLOGY OF CANCER –CANCER CAUSES –CANCER TYPES –GENES IN CANCER –TREATMENT SCHEMES

P-GLYCOPROTEIN

–HISTORY –STRUCTURE –LOCALISATION OF Pgp IN NORMAL TISSUES

Pgp SIGNIFICANCE ON THE THERAPY OF CANCER

–DRUG RESISTENCE –P-GP EXPRESSION IN CANCER CELLS

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PHARMACOLOGICAL TARGETING OF Pgp

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TO 3

GENERATION Pgp INHIBITORS –STEM CELLS AND CANCER GENE THERAPY

CONCLUSIONREFERENCES

THE BIOLOGICAL AND CLINICAL SIGNIFICANCE OF P-GLYCOPROTEIN IN CANCER

ABSTRACT

Cancer is a leading cause of death worldwide. It is characterized by rapid andunregulated growth of the body’s cells as a result of a mutation in a proto-oncogeneor a tumor suppressor gene or both. It is however resultant of multiple mechanismleading to its development ranging from environmental factors to hereditaryinfluence. The membrane bound MDR1 gene product P-glycoprotein (Pgp) has beenreported to be associated with drug resistance incidence in cancer to chemotherapy.Pgp is thought to have an evolutionary role as a protective mechanism against toxinsingested or inhaled from the environment. Pharmacological and gene therapyresearch has strived to modulate the effects of Pgp or more recently make use of thisdrug resistant characteristic for chemoprotection respectively.

Background

According to the World Health Organisation (WHO), cancer is a leading cause of death worldwide and accounts for an estimated 7.4 million deaths (2004 statistics),13% of all deaths worldwide. Cancer can affect any part of the body and there areapproximately 200 different types of cancer. (Cancer Research UK)In the U.K alone there are approximately 285,000 new cases of cancer diagnosedeach year and it is estimated that 1 in 3 people will develop some form of cancer intheir lifetime. It is non-discriminate of age however it is most prevalent in older peoplewith 75% of cases developing in people at the age of 60 and above. Cancers inchildren, teenagers and young adults account for approximately 1% of all cases.Although cancer incidence has remained relatively stable over the last decade therehas been an overall increase in incidence rates in the U.K constituting a rise of onequarter since 1975.

Table 1: Main types of cancer leading to mortality each year