Molecular Therapies and Ethics of Screening

Question 1

What leads to cancer cell growth?

Answer 1

Cancer cells don’t respond normally to these control mechanisms - independent of cell cycle control.
Leads to uncontrolled proliferation of transformed cells, which have the potential to invade other tissues, causing many problems.
Virtually any cell type may be transformed into a tumour cell.
Transformation is due to mutations - either spontaneous or due to the action of external agents (carcinogens).

Question 2

Why are cancer cells said to be immortal?

Answer 2

In vivo, or grown in tissue culture, cancer cells can go on dividing indefinitely

Question 3

What are HeLa cells?

Answer 3

cells of the HeLa cell line have been in continuous cell culture since 1951!
Cells of this cell line originate from a tumour removed from a woman called Henrietta Lacks

Question 4

How many times do cells usually divide before apoptosis?

Answer 4

20-50

Question 5

Describe the sequence of events that leads to cancer

Answer 5

Cancer begins when a single cell in tissue undergoes transformation.
The immune system normally recognises a transformed cell and destroys it
However, if the cell escapes destruction it can proliferate and form a tumour (a mass of abnormal cells in otherwise normal tissue)
If the tumour remains in the original tissue and is encapsulated it is called benign. Most not serious - can be removed by surgery.
Malignant tumours are invasive and can cause dysfunction of one or more organs.
An individual with a malignant tumour is said to have cancer.

Question 6

What is metastasis?

Answer 6

The spread of cancer cells to areas of the body that are distant from the primary tumour

Question 7

What is a mutation?

Answer 7

This mutation can be a random, spontaneous mutation, or be caused by a mutagen. Such mutagens may be chemical carcinogens, X-rays, UV, or viruses

Question 8

What percentage of cancers do viruses cause and give an example

Answer 8

15%

Papilloma viruses

Question 9

What are oncogenes?

Answer 9

Early researchers made a breakthrough when they found that tumours induced by viruses were caused by cancer-causing genes

Question 10

What are proto-oncogenes?

Answer 10

These genes were found to code for proteins involved in the normal cell cycle.

Question 11

Why would a proto-oncogene, a normal gene, become a potentially cancer-causing oncogene?

Answer 11

An oncogene arises from genetic changes. May be an increase in the production of the proto-oncogene’s protein product or a change in the protein’s activity. Either will have an effect on normal cell growth.

Question 12

What are tumour suppressor genes?

Answer 12

Genes that prevent cancer by inhibiting cell division

Question 13

What are the functions of the products of tumour suppressor genes?

Answer 13

1. Repair of damaged DNA which serves to prevent the accumulation and passing on of cancer-causing mutations
2. Control of cell adhesion to other cells or to the extracellular matrix (proper cell anchorage is important in normal tissue
3. Some proteins are part of the cell-signalling pathways that inhibit the cell cycle.

Question 14

Outline the role of ras proto-oncogenes and p53 tumour suppressor gene in cancer

Answer 14

These genes often found to be mutated in cancer.
The Ras gene is found to be mutated in about 30% of human cancers, while the p53 gene is mutated in nearly 50% cases!
Both the Ras and p53 proteins are part of the signal-transduction pathways that convey external signals to the DNA in the cell nucleus.
A growth factor binds to a receptor on the cell surface, causing a cascade of proteins.
The result is active transcription of a gene, producing a protein that is part of the normal cell cycle.

Question 15

True or False. Ras protein is a G protein?

Answer 15

True

Question 16

What are G proteins and how do they work?

Answer 16

G proteins relay growth signals from growth factor receptors to a protein kinase cascade
Cellular response at end of cascade is synthesis of protein that stimulates cell cycle and growth
Normally the pathway is inactive unless triggered by growth factor
Point mutation of the Ras gene may lead to overactive Ras protein

Can cause a cascade on its own
Cell division even in absence of growth factor
Overactive or excess amounts of Ras cause excessive cell division

Question 17

Why is p53 gene referred to as “guardian angel of the genome”?

Answer 17

The tumour-suppressor p53 gene promotes the production of growth inhibiting proteins.
The p53 gene is known as the “guardian angel of the genome”. Damage to DNA leads to p53 gene expression
The P53 protein acts as a transcription factor for several genes, often the p21 gene which halts the cell cycle.
This allows time for the cell to repair the damaged DNA.
Also p53 activates “suicide genes” encoding proteins for apoptosis
This activation of suicide genes occurs if the DNA damage is irreparable
All these mechanisms stop a cell passing on mutations due to DNA damage
If p53 gene is mutated or missing mutations can be passed on through cell division and cancer may ensue.

Question 18

Explain how polyps turn cancerous

Answer 18

The development a polyp to tumour is caused by a gradual accumulation of mutations.
These mutations gradually activate oncogenes and de-activate tumour-suppressor genes
The Ras oncogene and a mutated p53 tumour suppressor gene are often involved
However, there are some changes that must occur for a cell to become fully cancerous:
First, there must be activation of at least one oncogene and the mutation or loss of several tumour-suppressor genes

Question 19

How is the use of antibodies important in the diagnosis of tumours?

Answer 19

Fluorescence or radio-labelled tumour-specific monoclonal antibodies can be used to detect tumour cells.

Question 20

What is the magic bullet approach for targeting tumour cells specifically?

Answer 20

Method uses tumour-specific antibody molecules linked to a cytotoxic drug.
Alternatively, using a similar approach, antibody fragments containing one tumour-specific domain and a domain that binds and activates receptors on cytotoxic T lymphocytes has been of some use.

Question 21

How is immunotherapy used in cancer treatment?

Answer 21

The use of Immunotherapy tries to boost the immune system to mount a stronger attack against cancer cells. Although most tumours express or contain proteins different from those present in normal cells, these are still regarded by the body as “host” cells and basically “host” proteins. There is a need to overcome this and stimulate the immune system.

Question 22

How can gene therapy be used in cancer treatment?

Answer 22

An example of an emerging new approach is gene therapy.
Gene therapy is a treatment where a patient’s affected cells’ genotype is altered by the addition or deletion of a specific gene.
A genetically engineered virus used to infect malignant cells with a normal version of the gene, called a therapeutic gene.
E.g. Adenovirus or naked injected DNA used to introduce growth factor in heart disease
Problems with placement of gene and control of gene expression
Ethical issues

Question 23

How is Ex vivo gene therapy being used to treat other genetic disorders?

Answer 23

Hypercholesterolemia
Certain forms of cancer
For example, using cells from a tumour with mutant tumour-suppressor p53 genes, the cells are grown in large numbers in vitro. The cells are then incubated with retroviruses containing normal versions of the p53 gene.
The transformed cells are then returned to the patient, hopefully returning expression of tumour-suppression protein activity.
So far, however, this technique has met with only limited success.

Question 24

Is it possible to test every person to see if they would be a carrier of a genetic disorder?

Answer 24

No

Question 25

What are the characteristics that would ethically allow genetic screening of patients?

Answer 25

Participation should be voluntary and informed (adult)
Disease should be common, severe enough to warrant an offer of prenatal diagnosis for couples who are both carriers
Test should be simple, cheap, specific and reliable