Introduction to hallmarks of cancer

Question 1

What is senescence and quiescence

Answer 1

senescence is irreversible cell cycle arrest driven by a number of different mechanism
quiescence is cells in the state of not dividing

Question 2

How does a normal cell transform tumorigenic cell

Answer 2

○ Disabling detection mechanisms
○ Inactivating negative cell cycle regulators
○ Overactivation of positive cell cycle regulators
○ Inactivating genome stability factors

Question 3

What are the major types of cancer

Answer 3

carcinomas, sarcomas, lymphomas, myelomas, leukemias

Question 4

What are the subtypes of carcinomas

Answer 4

adenocarcinoma in lung, breast, prostate and colon cancer

Squamous cell carcinoma or skin cancer

Question 5

Where do sarcomas arise

Answer 5

in supporting tissues of body

Question 6

where do lymphomas arise and what are the main types

Answer 6

arise in WBC and are divided into hodgkin’s lymphoma and non-hodkin’s lymphoma

Question 7

where do myelomas arise

Answer 7

in antibody-producting plasma cells

Question 8

where do leukemias arise and what are the main types

Answer 8

they arise in immature blood cells that grow in BM and accumulate in blood stream
can be categorised into actue leukemia, chronic leukemia, lymphocytic (affect lymphocyte), myelogenous leukemia (affect other cell types )

Question 9

what are the main cause of cancer

Answer 9

tobacco, virus such as HPV, Hepatitis B and C

bacterial infection such as H.pylori and ageing, UV light

Question 10

What are the six hallmarks of cancer

Answer 10

evading apoptosis
self-sufficiency in growth signals 
insensitivity to anti-growth signals 
tissue invasion and metastasis
limitless replicative potential 
sustained angiogenesis

Question 11

What cell types are linked to cancer

Answer 11

Cancer stem cells – progenitor cells from which the tumour is derived
• Immune inflammatory cells – innate immune cells that secrete growth factors and
cytokines that promote tumorigenesis
• Cancer associated fibroblast – cell that secretes paracrine factors to promote
tumorigenesis
• Endothelial cells – form the blood vessel walls
• Pericyte – wrap around endothelial layers to regulate capillary blood flow
• Invasive cancer cells – cells that acquire the ability to move out of the original
tumour site

Question 12

What three mechanism can cells undergo for self-sufficiency in growth signals

Answer 12

Alteration of extracellular growth signals - Cancer cells acquire the ability to make their own growth factors, creating a positive feedback signalling loop

Alteration of response to growth factors - cancer cells overexpress receptors that allow them to become hyper-responsive to levels of growth factors that would not normally trigger growth.

Alteration of intracellular response - I n some cancer cells, the downstream cytoplasmic components that receive and process growth factor signals can signal without ongoing stimulation by their normal upstream regulators.

Question 13

Describe insensitivity to anti-growth signals

Answer 13

In cancer cells, when DNA is damaged, RB is damaged which is a tumour suppressor and cannot activate the checkpoint and damaged cell will continue to divide - avoiding apoptosis

Question 14

Describe evading apoptosis

Answer 14

cells avoid apoptosis due to absent or defective p53

Question 15

Describe limitless replicative potential

Answer 15

cells have a hayflick limit where they become senescent

cancer cells upregulate telomerase to avoid telomere shortening and triggering of senescence

Question 16

Describe sustained angiogenesis

Answer 16

process which cells trigger formation of new blood vessels so tumour can grow and spread
tumours release VEGF to activate endothelial cells to form new blood vessels

Question 17

What are the stages in tumour progression pathway in sustained angiogenesis

Answer 17

1. dormant- tumour start growing as avascular nodules until they reach stead state level of proliferating and apoptosing cells
   
   2. Perivascular detachment and vessel dilation
      ○ The initiation of angiogenesis, or the ‘angiogenic switch’, has to occur to ensure exponential tumour growth.
      ○ The switch begins with perivascular detachment and vessel dilation.
   3. Onset of angiogenic sprouting
      ○ Perivascular detachment and vessel dilation is followed by angiogenic sprouting
      ○ Continuous sprouting; new vessel formation and maturation; Recruitment of perivascular cells
      ○ New vessels form and mature, and there is recruitment of perivascular cells
      ○ Tumour vasculation
      ○ Blood-vessel formation will continue as long as the tumour grows, and the blood vessels specifically feed hypoxic (areas where there is inadequate oxygenation) and necrotic (dying) areas of the tumour to provide it with essential nutrients and oxygen.

Question 18

describe metastasis

Answer 18

cancer cells can invade surrounding tissues and vessels and transported by circulaory and reinvade and grow in new location

Question 19

How do cell carry out metastasis

Answer 19

· In order to break away from tumour
○ Cell overcome mechanisms that cause them to adhere to their neighbours
○ Adhesion such as e-cadherin is downregulated in cancer
may also alter expression of integrin protein

Question 20

What is the 7th hallmark and its characteristics ?

Answer 20

Deregulating cellular energetics
· Warburg effect - even in the presence of oxygen, cancer cells can reprogram their glucose metabolism and thus their energy production, by limiting their energy metabolism largely to glycolysis, rather than the much more efficient oxidative phosphorylation pathway
○ Leading to aerobic glycolysis
· Leads to increased generation of additional metabolites that benefit proliferating cells

Question 21

What is the 8th hallmark and its characteristics ?

Answer 21

Avoiding immune destruction

· By switching off the expression of cell surface antigens that would identify them to the immune system as dangerous

Question 22

What are the two enabling characteristics

Answer 22

genome instability and tumour-promoting inflammation

Question 23

describe genome instability

Answer 23

DNA methylation to inactivate tumour suppressor genes

eg. BRCA1 and/2, p53 and Rb which are involved in DNA repair, halting cell cycle upon DNA damage

Question 24

Describe tumour promoting inflammation

Answer 24

· Supplies bioactive molecules to tumour microenvironment, including growth factors to sustain proliferative signalling
· Release ROS which are actively mutagenic