hallmarks of cancer

Question 1

what things has the study of cancer made us know more about?

Answer 1

growth of normal cells
pathways controlling normal growth
mechanisms of cell death
mechanisms of tissue regeneration

Question 2

what does cancer imply?

Answer 2

• uncontrolled growth
• capacity to infiltrate or damage normal tissues
• capacity to spread to other sites
• capacity to cause illness and/or death

Question 3

what are the 6 hallmarks of cancer

Answer 3

1. autonomy from growth signals
2. evasion of growth inhibitory signals
3. evasion of apoptosis
4. unlimited replicative potential
5. angiogenesis
6. invasion and metastasis

Question 4

where do mutations have to occur for cancer to be inherited?

Answer 4

germline

Question 5

which viral infections are associated to which cancer?

Answer 5

HPV 16 & 18 - cervical carcinoma

HTLV-1 - adult T cell lymphoma

EBV - Burkitt’s lymphoma

Hepatitis B & C - hepatocellular carcinoma

Question 6

why can chemotherapy and chemical carcinogens cause cancer?

Answer 6

• interact with components of DNA to cause damage
• damage may be to bases or sugar-phosphate backbone
• damage may be repaired, misrepaired or unrepaired
• unrepaired or misrepaired damage that does not trigger cell death will be passed on to daughter cells

Question 7

what do oncogene mutations lead to?

Answer 7

• affect expression of proteins involved with pathways associated with cancer
• pathways for growth differentiation and cell death
• mutated genes and their products become overactive

Question 8

what type of mutation occurs in tumour suppressor genes in cancer?

Answer 8

loss of function

Question 9

what are oncogenes?

Answer 9

oncogenes are often mutated versions of normal human genes (proto-oncogenes)

mutations may affect gene function in various ways

Question 10

what are the effects of oncogenes

Answer 10

increase activity of pro-malignant pathways:
cell growth, replication, angiogenesis
invasion, metastasis

inhibit activity of anti-malignant pathways:
apoptosis, cell cycle regulation, growth inhibition

Question 11

what are 3 examples of oncogenes?

Answer 11

1. erbB1 encodes the EGFR receptor-> result is over-activity of RAS - MAPK pathway and over-expression of growth promoting genes
2. erbB2 is amplified in about 25% of breast cancers
   Her2 is over-expressed in these cancers
3. Ras- mutated in 30% of cancers

Question 12

what is the inheritance pattern of oncogenes?

Answer 12

dominant

Question 13

what is the inheritance pattern if tumour suppressor genes?

Answer 13

recessive

Question 14

what are 2 tumour suppressor genes?

Answer 14

• P53 mutated in 1/2 cancers

- APC- FAP and increased colorectal cancer

Question 15

what syndrome do you get with mutated gremlin p53?

Answer 15

Li-Fraumeni syndrome:

grossly elevated cancer risk
sarcoma, breast cancer, leukaemia, brain tumours at an early age

Question 16

what doe APC mutation inhibit?

Answer 16

B- catenin

results in proliferation

Question 17

what are the 3 gees associated with apoptosis?

Answer 17

Bcl-2 anti-apoptotic
Bax pro-apoptotic
p53 pro-apoptotic

Question 18

how do cancer cells gain unlimited replicative potential?

Answer 18

• telomerase inactive in most normal tissues
• telomerase upregulated in most tumour cells- increasing size of telomeres reduces the chance of cell senescence
• proteins that activate telomerase contribute to malignant transformation

Question 19

how are cancer cells able to induce angiogenesis?

Answer 19

angiogenesis stimulated by hypoxia in normal tissues and tumours

Vascular Endothelial 
Growth Factor (VEGF) major stimulant 
VEGF upregulated in many tumours

Question 20

how are cancer cells able to invade and metastasise?

Answer 20

-tumour cells can break free from inter- and extra-cellular connections via abnormal expression of integrins

invasive capacity mediated by matrix metalloproteases (MMPs) and inhibited by TIMPs - abnormal balance in tumour cells

Question 21

what are 2 emerging hallmarks of cancer?

Answer 21

1. deregulating cellular energetics

2, avoiding immune destruction

Question 22

what are 2 enabling characteristics of cancer?

Answer 22

• genome instability

- tumour promoting inflammation