Chapter 16, Problem 1CS

CASE STUDY| I thought it was safe

A middle-aged woman taking the breast cancer drug Tamoxifen for ten years became concerned when she saw a news report with disturbing information. In some women, the drug made their cancer more aggressive and more likely to spread. Other women with breast cancer, the report stated, do not respond to Tamoxifen at all, and 30 to 40 percent of women who take the drug eventually become resistant to chemotherapy. The woman contacted her oncologist to ask some questions:

How can some people react one way to a cancer treatment and others react a different way?

Summary Introduction

Case summary:

A middle-aged woman was taking Tamoxifen drug as breast cancer treatment for 10 years. One day she came across a disturbing news, which said that different response was seen in different patients as this drug made cancer more aggressive and metastasize in the rest of the body in some patients. While other woman did not respond to the drug and 30–40% of women gradually became resistant to chemotherapy. The woman had some queries to be asked by her oncologist.

Characters in the case:

A middle-aged woman suffering from breast cancer for 10 years.

Adequate information:

The news report points out the different response of the patients to breast cancer treatment, in which some patient’s cancer has aggravated, few others do not show any response to the treatment, and around 40% have become resistant to chemotherapy.

To determine:

The reason for the different responses by different individuals for the drug to cancer treatment.

Explanation of Solution

Given information:

The drug for cancer shows variation in response in different group of individuals.

All the drugs designed for cancer treatment are DNA (deoxyribonucleic acid) damaging. The uncontrolled proliferation of cell is due to mutated DNA, which has to be destructed in order to inhibit tumor growth.

Pharmacogenomics is the field that studies the interaction of medicine with inherited genes. Although the same chemical agent is used as a drug for cancer therapy in all patients, even then different patients react differently to it, the following could be the reasons:

1. The different individual possesses different gene composition: The basic genome structure of all the individuals are same but the great diversity between the individuals of the same species is introduced due to 0.1% difference in genetic makeup. Thus, different cell lines react differently to the same drug.

2. The difference in the rate of metabolism: Different individuals have a different rate of metabolism. Few individuals may break down the drug fast as compared to another individual, making the treatment successful. Another individual may gradually metabolize the drug and the drug may persist for a long time in their body, this would not only cause adverse side effects but also may not give any response to the treatment.

3. The difference in drug activation and deactivation: On receiving a particular drug, certain enzymes are synthesized in the body, which helps in the activation of this drug but the drug activation does not occur in all the individuals. Similarly, drugs also need to undergo deactivation to inhibit the exposure to the healthy cells and limit the side effect of the drug.

4. The difference in DNA repair pathway: Once the DNA-damaging drugs are introduced, the cells will defend itself against the damage of DNA caused by chemotherapeutic drugs. The defense mechanism of cells includes DNA repair and other pathways but due to the difference in genetic makeup, every individual will have a slight variation among the genes involved in these pathways.

Conclusion

Therefore, it can be concluded that the basic composition of the genome is same in each and every individual but the great diversity, which is seen among individuals of same species, occurs due to a slight difference in the genetic makeup. The difference in response to cancer treatment is due to this difference in cell line or genes.