Cancer Patients, Chemotherapy, and Drug Resistance

Some chemotherapy patients have been shown to develop a resistance to therapeutic drugs. The genes responsible for this resistance may also 'drive' tumor growth (1). A study conducted in 1995 found that drug resistant cancer tissue contained an over abundance of two enzymes which protect cancer cells from death (2). Drug resistance can be induced by the drug itself or acquired without prior induction. Susceptible cancer patients run the risk of tumor promotion within drug resistant tissues when undergoing chemotherapy.

There are various mechanisms known to convey drug resistance in the chemotherapy patient:

Specific resistance to a selected drug can occur by deletion of the necessary activation enzyme for that drug such as deoxycitidine kinase for the drug cytosine arabinoside (3).

A general type of resistance is the over-expression of a drug efflux pump in the cell such as P-glycoprotein (pump) which, conveys resistance to a broad array of natural products used in cancer treatment.

Mutations in genes such as, the p53 suppressor oncogene may lead to drug resistance. A suppressor gene is necessary for controlling the proliferation of normal cells; it controls their life cycle, including reproduction. The loss or mutation of this type of gene allows cells to undergo malignant transformation and can inactivate programmed cell death (apoptosis). This leads to the continuous proliferation and survival of highly mutated cells (3).

Current research is focusing on the restoration of apoptosis, which is correlated to the cell's sensitivity to drugs.

It has been shown that combining drug therapies which have different mechanisms for fighting cancer is the more effective method for fighting cancer.

For a discussion on the development of Cancer, click here.

References

1. Kerbel RS, Kobayashi H, Graham CH. 1994. Intrinsic or aquired drug resistance and metastasis: are they linked phenotypes? Journal of Cellular Biochemistry, Sep 94, 56(1) :37-47.

2. Eliopoulos AG, Kerr DJ, et al. 1995. The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2. Oncogene, Oct. 5, 11(7) :1217-28.

3. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Ninth Ed. Edit. by Molinoff and Ruddon. McGraw-Hill, New York.

This page was prepared by Theresa L. Pedersen, UCD EXTOXNET FAQ Team. August 1997.