AETIOLOGY OF CANCER 2

Question 1

why are cancer cells called selfish cells?

Answer 1

they have have a selective advantage over normal, regulated cells – a form of natural selection

Question 2

why are tumours said to have a ‘life of their own’?

Answer 2

Increase in neoplasm size persists whilst the hosts body is wasting (cachexia)
Ultimately kill themselves by killing the host

Question 3

how do cancer cells and normal cells differ?

Answer 3

Growth control
Contact inhibition
Repair/death mechanisms
Metastatic ability
Appearance
Growth rate
Maturity/differentiation
Immune evasion
Function
Angiogenesis

Question 4

how can you measure tumour growth?

Answer 4

amount of time it takes the cell mass to double in size, and the number of such ‘doublings’

Question 5

what is carcinogenesis?

Answer 5

process of inducing cancer

Question 6

what kind of process is carcinogenesis?

Answer 6

A multistep process

Question 7

what does carcinogenesis involve?

Answer 7

A normal cell evolves progressively to a cancerous state through acquiring a succession of properties
A normal cell acquires a series of molecular changes which result in the cell having new properties

Question 8

what molecular changes does a cancer cell acquire?

Answer 8

changes to its DNA (genetic material) and to the proteins it produces

Question 9

what is a change to DNA called?

Answer 9

mutation

Question 10

define hallmarks

Answer 10

small number of traits

Question 11

what are hallmarks?

Answer 11

traits that are shared by all cancers that govern the transformation of normal cells into cancerous ones

Question 12

what are the 6 original hallmarks?

Answer 12

• sustaining proliferative signalling
• evading growth suppressors
• activating invasion and metastasis
• enabling replication immortality
• inducing angiogenesis
• resisting cell death

Question 13

what does sustaining proliferative signalling involve?

Answer 13

Normal cells need external signals from growth factors to divide
Cancer cells are not dependent on normal growth factor signalling
Acquired mutations `short-circuit’ growth factor pathways leading to unregulated growth

Question 14

give an example of ustaining proliferative signalling

Answer 14

mutation in Ras oncoprotein disrupts the normal -ve feedback mechanisms that dampen a signalling pathway when a mitogenic signal is hyperactivated

Question 15

what does evading growth suppressors involve?

Answer 15

Normal cells respond to inhibitory signals
Cancer cells do not respond to growth inhibitory signals
Acquired mutations interfere with inhibitory pathways

Question 16

give an example of evading growth suppressors

Answer 16

p53 is a common tumour suppressor gene which is inactivated in cancer cells leading to uncontrolled growth and proliferation

Question 17

what does resisting cell death involve?

Answer 17

Apoptosis
Normal cells are removed by apoptosis, often in response to DNA damage
Cancer cells evade apoptotic signals

Question 18

give an example of resisting cell death

Answer 18

dysregulation of anti-apoptotic BCL-2 family members

Question 19

what does enabling replicative immortality involve?

Answer 19

Normal cells have a finite number of cell divisions after which they become senescent
The `cellular counting device’ is the shortening of chromosomal ends (telomeres) that occur after every round of DNA replication

Question 20

what do cancer cells do in enabling replicative immortality?

Answer 20

Cancer cells maintain the length of their telomeres

Altered regulation of telomere maintenance results in unlimited replicative potential

Question 21

give an example of enabling replicative immortality

Answer 21

Overexpression of telomerase allows tumour cells to overcome finite replicative ability

Question 22

what does inducing angiogenesis involve?

Answer 22

Normal cells depend on established BV to supply oxygen and nutrients
Cancer cells induce angiogenesis, the growth of new BV, needed for tumour survival and expansion

Question 23

give an example of inducing angiogenesis

Answer 23

Tumour angiogenesis is a function of multiple signals from a number of cell types residing in the tumour microenvironment

Question 24

what does activating invasion and metastasis involve?

Answer 24

Normal cells maintain their location in the body and generally do not migrate
Cancer cells can move to other parts of the body and start secondary tumours

Question 25

how does cancer grow?

Answer 25

Cells of malignant tumour duplicate rapidly and invade surrounding tissue (break through basement memb) triggers angiogenesis through production of (TAFs)

Question 26

how does cancer spread?

Answer 26

Cells compete with normal tissue for space and nutrients and eventually kills them Some cells detach from primary tumour, enter body cavity or blood and establish secondary tumours

Question 27

what are the 4 modes of tumour spread?

Answer 27

Local invasion Lymphatic spread Vascular spread Trans-coelomic spread

Question 28

what is the difference between malignant and benign tumours?

Answer 28

benign tour cells grow only locally and can't spread by invasion or metastasis malignant cells invade neighbouring tissues, enter BV, and metastasise to different sites

Question 29

what are the 4 steps in the metastatic process?

Answer 29

Motility and invasion from the primary site – can be as single cells or clumps Embolism and circulation in blood or lymph system – can also get spread through fluids in a body cavity Arrest in a distant capillary & adherence to the endothelium Extravasation into the target organ parenchyma

Question 30

what do tumours need to metastasise?

Answer 30

they need an external stimulus through molecular cross-talk with cells in the neoplastic environment

Question 31

what is EMT?

Answer 31

Epithelial mesenchymal transition

Question 32

what is EMT involved in?

Answer 32

wound repair | metastasis

Question 33

what does genome instability & mutation involve?

Answer 33

Cancer cells generally have severe chromosomal abnormalities, which worsen as the disease progresses These genetic alterations drive tumour progression

Question 34

how do cancer cells promote genome instability?

Answer 34

they take advantage of mutations in DNA repair pathways

Question 35

what has been found to induce many types of cancer?

Answer 35

local chronic inflammation

Question 36

what do inflammatory cytokines promote?

Answer 36

tumour growth, proliferation and angiogenesis

Question 37

how does tumour-associated inflammation promote tumour growth?

Answer 37

by supplying the microenvironment with growth factors, survival factors, and factors that promote angiogenesis

Question 38

how are cancer cells seen by the body?

Answer 38

they appear to be invisible to the body’s immune system

Question 39

how do cancer cells avoid immune destruction?

Answer 39

by disabling components of the immune system that have been dispatched to eliminate them recruitment of inflammatory cells that are actively immunosuppressive

Question 40

how do cancer cells generate energy?

Answer 40

use abnormal metabolic pathways

Question 41

how do cancer cells produce energy?

Answer 41

by a high rate of glycolysis followed by lactic acid fermentation in the cytosol

Question 42

what is the warburg effect?

Answer 42

Cancer cells convert available glucose to lactate irrespective of the availability of oxygen

Question 43

what does the warburg effect lead to?

Answer 43

they divert glucose metabolites to useful anabolic processes that accelerate cell proliferation

Question 44

what is the tumour stroma?

Answer 44

Cells co-opted in to supporting the cancer

Question 45

what does the tumour stroma contain?

Answer 45

vascular elements fibroblasts macrophages

Question 46

what do vascular elements do?

Answer 46

provide growth factors, blood supply (oxygen, nutrients)

Question 47

what do fibroblasts do?

Answer 47

contribute MMPs for extracellular matrix degradation during cancer cell migration

Question 48

what do macrophages do?

Answer 48

(alternatively activated), may provide defence against immune surveillance

Question 49

what are the causes of cancer?

Answer 49

carcinogens viral infections oncogenes

Question 50

what are carcinogens?

Answer 50

chemical agent or radiation that causes cancer eg. hydrocarbons, UV

Question 51

what are oncogenes?

Answer 51

cancer causing cells

Question 52

where are oncogenes derived from?

Answer 52

from proto-oncogenes (normal genes)

Question 53

what do porto-oncogenes do?

Answer 53

regulate normal growth and development

Question 54

what are carcinogenic agents?

Answer 54

chemicals radiation microbiologicals

Question 55

what are chemical carcinogenic agents?

Answer 55

Some direct acting but most require metabolic conversion (procarcinogens)

Question 56

what are radiation carcinogenic agents?

Answer 56

Hard uv light, X-rays, ß, gamma

Question 57

what are microbiologicals carcinogenic agents?

Answer 57

RNA viruses-leukaemia DNA viruses- Kaposi’s sarcoma Pathogenic species- gastric carcinoma and lymphoma

Question 58

give examples of carcinogens

Answer 58

Percival Pott Soot Tobacco smoke

Question 59

give examples of cancers

Answer 59

``` chronic myelogenous leukaemia cervical cancer breast cancer melanoma retinoblastoma ```

Question 60

what are the different treatments of cancer?

Answer 60

Surgery, chemotherapy, radiotherapy, biological - individually or in combination

Question 61

what are the side effects of radiation therapy?

Answer 61

hair loss, nausea and vomiting (destructive effect on hair follicles and lining of stomach and intestine)

Question 62

why does radiation therapy increase susceptibility to infection?

Answer 62

due to slow production of WBCs in bone marrow

Question 63

why is treatment of cancer difficult?

Answer 63

as cancer contains diverse population of abnormal cells varying in their resistance to drugs