Cancer

Question 1

What are the hallmarks of a malignant tumour? (10 points)

Answer 1

• Cancerous
• Grows rapidly (uncontrolled preliforation)
• Uncapuslated
• Invasive (they grow beyond their defined barieirs - i.e the cells loose structure and organization and invade locally by infiltration + they invade other sites by metastatic spread).
• Loss of function due to inability to differentiate. (cells have lack of differentiation)
• Consists of different types of cells because of multiple mutations that occur.
• Ability to metastasize (i.e it can break off and travel to other areas and organs of the body and cause tumours in those areas).
• Very Dangerous
• More likely to recur
• cells lose contact inhibition

Question 2

What are the hallmarks of a benign tumour? (9 points)

Answer 2

• NOT cancerous
• grows slowly (controlled preliforation)
• often encapsulated - i.e they have a well defined capsule
• Non-invasive (do not invade locally or metastasise)
• consists of cells that are similar to the source tissue
• no ability to matastasize (i.e it does not break off and travel to other areas or organs) BUT - benign tumours can become malignant (e.g adenoma of the large bowel may become an adenocarcinoma).
• relatively local
• cells do not lose contact inhibition
• Not really dangerous (as long as they are removed before they might compress vital tissue and organs e.g bening brain tumours).
• Once removed, unlikely to recur.

Question 3

When is hormonal therapy used and what is the aim of it?

Answer 3

Hormonal therapy is used to treat specific cancers. They are specifically used with tumours that are affected by hormones (for example ovarian cancer, or testicular cancer).
The aim of hormonal treatment is to ‘starve’ the cells of signals that would stimulate cell division.

Question 4

How/why does hormonal treatment work?

Answer 4

Hormonal signals (eg. insulin and oestrogen) are the way by which cells communicate to effect a change in cellular behaviour e.g growth and reporduction of target cells.
Cancer cells, while abnormal still respond to such signals stimulating division. So hormonal treatment essentially blocks/inhibits the hormones that would stimulate the cells to divide.

Question 5

Is hormonal treatment used alone?

Answer 5

It can be, but hormonal (adjuvant) therapy is often used in combination with other treatments. Different groups antagonise different signal pathways.

Question 6

What does Imatinib mesylate ‘Glivec’ do, and for which cancer is it used as part of treatment?

Answer 6

1. It blocks specific processes in cell growth signals.

2. it is used for Chronic Myeloid Leukaemia (CML)

Question 7

What does Gefinitib ‘Iressa’ do and for what type of cancer is it used as part of treatment?

Answer 7

1, It blocks epidermal growth factor receptor (EGFR) which is over expressed in many cancers.
2. Used for non small cell lung cancer.

Question 8

What is an exciting new development in treatment which targets cancer cells? What do they aim to do? What are their limitations? (3 points)

Answer 8

1. Specific Inhibitors.
2. They aim to ‘target’ cancer specific oncogenic pathways and processes instead of processes that may be common to all cells with the resulting side effects.
3. These drugs have the potential to be highly specific and not be directly toxic only targeting cancer cells.
4. That being siad, the specifity many not be enough to kill, only slow down the cancer cells. So these may be used with conventional chemotherapy.

Question 9

What are some examples of Specific inhibitors?

Answer 9

1. Imatinib mesylate ‘Glivec’ (used with CML)

2. Gefinitib ‘Iressa’ (used with non small cell lung cancer)

Question 10

What are some examples of new ‘target’ therapies (immunotherapies)? and what do each of them do? (3 points)

Answer 10

1. Immunotherapies - (to help the body recognise cancer cells and strengthen the responses that will destroy cancer)
2. Cancer vaccines (i.e ‘active’ specific immunotherapies) - (to stimulate the body’s own immune system to fight the disease).
3. Monoclonal antibody therapy (i.e passive immunotherapies) - (do not rely on the body’s own immune system but use immune system components, such as antibodies, created outside the body (e.g Tratuzumab ‘Herceptin’).

Question 11

What are some other examples of new therapies to treat cancer? What do they involve? (2 points)

Answer 11

1. Photodynamic therapy = A new treatment involving a photosensitising agent that makes cells more sensitive to light and, by doing so, causes cancer cells to be destroyed when a laser light is directed on a cercerous area.
2. Thalidomide (Background: This drug was well known in the 1960s for its use in treating sickness in pregnancy, resulting in birth defects. These defects were caused by the thalidomide’s ability to interfere with the development of new blood vessels).
   SO as a cancer treatment, researchers are hoping to use the drug to prevent cancers from developing new blood vessles (angiogenesis) thereby starving the cancer of oxygen and nurtients and causing the tumour to shrink.

Question 12

Have we been making progress when it comes to fighting cancer? how has the death rate changed?

Answer 12

1. Athough the incidence and prevalence of cancer appears to be increaing (probably because people are living longer), the death rate is falling.
2. Increasingly people now LIVE with, rather than DIE from cancer.

Question 13

What are proto-oncogenes?

Answer 13

extremely important genes involved in regulation of cell growth.

Question 14

What is the research vision for cancer treatment?

Answer 14

To develop anticancer drugs targeted to each hallmark capability to revent or eliminate cancers.

Question 15

What are the 4 most common sites of metastatic deposits?

Answer 15

Lungs, bones, brain and liver.

Question 16

What are the four ways/routes by which metastatic invasion (spread) may occur?

Answer 16

1. Via the lymphatic system
2. Via the bloodstream
3. Via serous cavities
4. Via the cerebrospinal fluid (CSF)

Question 17

How do cells in the body normally behave? How is cell growth, division and death controlled? what happens with cancer?

Answer 17

1. Under normal circumstances, cell division in an adult takes place only when signals indicate the need to grow or to replace cells that have been lost, damaged, or worn out. Cell division, Cell death and differentiation - are tightly regulated by many signals and signal pathways.
2. To maintain functional cells through cell division the normal regulatory function of the cell will employ chemical signals to drive and halt growth; this is controlled by genetic components of the cell.
   - The chemical signals act within individual cells and are also utilized when communicating with neighbouring cells in regulating growth.
3. The genes involved with regulation of cell growth are called proto-oncogenes. (these have the ability to switch on/promote cell growth).
   - When one of these genes becomes damaged and permanently switched on it is referred to as an oncogene.
4. The ability of the cell to inhibit/switch off growth is regulated by a tumour supressor gene.
   - When this gene is damaged the function is lost and the cell can no longer switch off growth.
5. Another gene implicated in the replication repair process is called the mismatched repair gene. This gene repairs damaged DNA after replication.
   - When this gene is damaged the cell accumulates lots of mismatched DNA which in turn promotes cell growth.
6. The last essential gene controls the process of apoptosis (programmed cell death) - which is what ensures that after a cell has divided a certain number of times it commits cell death.
   - Damage to this gene results in an inability to programme the cell to die.

• Such damage may occur from either error in DNA replication during mitosis or exposure to environmental agents.
• In the transformation to a cancerous growth, there is a progressive series of mutations of genes regulating cell division and differentiation.
• When multiple mutations affecting these regulatory mechanisms accumulate in a single cell, the cell will lose all control with respect to cell division. This single cell, dividing repeatedly and without regulation will create an ever expanding clone of cells which will also undergo unregulated cell division. This is the essence of cancer.

Question 18

What are the aquired capabilitis of cancer cells which mean that they are able to evade normal controls and prolliferate uncontrolably? (6 points)

Answer 18

1. Self suffficiency in growth signals (GS); autonomy modulated by oncogenes.
2. Insesitivity to antigrowth factors/signals (that regulate cell advance through the G1 phase)
3. Evading apoptosis (programmed cell death) often associated with deactivation of p53.
4. Limitless replicability as a result of the above, leading to deregulated proliferation.
5. Sustained angiogensis via an ‘angiogenic switch’ at an early or mid-stage event in cancers.
6. Tissue invasion and metastases which depend upon all of the above capabilities.

Question 19

How does cancer (a malignant tumour) develop from one mutated cell? what is the basic process of tumourigenesis? (6 points)

Answer 19

1. Cell mutation incactivates tumor suppressor gene
2. Cells proliferate
3. Mutation of proto-oncogene creates an oncogene
4. Mutation inactivates several more tumor suppressor genes
5. Cancer/i.e malignant neoplasia

Question 20

What are the 6 main steps (clue = Key words) in the development of a cancer to become an invasive neoplasia, after one cell has transformed and become cancerous?

Answer 20

1. Causes abnormal development or changes to occur in the tissue (i.e Dysplasia)
2. As cancer cells proliferate rapidly, the tissues develop and become a neoplasia/tumour (composed of a variety of cancer cells due to continuous mutation)
3. Cancer cells secrete angiogenic factors, namely, VEGF, PDGF and BFGF which bind to receptors on the epithelial cells of blood vessels –> this is what stimulates angiogenesis (new vessel formation).
4. New blood vessels start to form and mature/develop (Angiogenesis) to supply nutrients and energy to these cancer cells.
5. Cancer cells proliferate even more to the point where they can become an invasive neoplasia.
6. Invasive neoplasia’s are very vascular. The new blood vessels form all around the tissue, and so cancer cells can penatrate through the tissue and into the blood vessels (i.e blood stream) where they will then travel round the body and can invade other tissues (metastasis).

Question 21

a) Where is stomach/colerectal cancer likely to metastasise? (1 point) b) What is the process involved in travelling from the primary site (stomach/colon) to the secondary site (?) ? (4 points)

Answer 21

a) The liver.

b) 1. Stomach/colon tumour cells enter and travel in blood.
2. the cells become enmeshed in nearest capllary network
3. the tumour cells reach the liver sinusoid and grow in liver substance
4. Liver metastases become established

Question 22

Generally, what are carcinogens and what role do they play in causing cancer? (Initiation?) (Promotion?)

Answer 22

Factors that both initiate and promote changes in the cell which lead to cancer. Both of these steps are required to cause the cancer.
Initiation = a mutagenic event occurs in the DNA of a single cell.
Promotion = repeated exposure to carcinogenic agents may or may not cause this initiated cell to proliferate to form a tumour.