fabian cancer biology slide 81-120 Flashcards

1
Q

What is the difference between a tumor suppressor and oncogene in terms of function?

A

-tumor suppressor=loss of function (cant add a drug to add function for missing/altered protein)
-oncogene is gain of function

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2
Q

How does synthetic lethality occur in cancer?

A

-if we have a gene B cancer mutation, then we are hyperdendent on gene A, but if Gene A gets inactivated then this will lead to cell death

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3
Q

What are the 2 benefits for using synthetic lethality based strategy?
What is it selective for, what can it be applied to?

A

-synthetic lethality is selective for cancer cell- specific genetic mutations.
This strategy can be applied to any type of cancer mutation, including tumor suppressors and mutations deemed ‘undruggable’

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4
Q

What are the DNA damage repair mechanisms for X-rays, Uv light and replication errors?

A

-x-rays/spontaneous rxn repair=base excision repair (BER)
-UV light =nucleotide excision repair (NER)
-X-ray/anti tumor=recombinational repair (HR homologous recomb or EJ)
-replication error=mismatch repair

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5
Q

What is an example of a synthetic lethal approach?
What is it an inhibitor for?
What is BRCA?

A

-The first synthetic lethal therapy using (poly(ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1-mutant or BRCA2-mutant ovarian and breast cancers)
-BRCA is a tumor suppressor gene

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6
Q

How do you screen for synthetic lethal interactions
What are you looking for?

A

-you use a Ras wild type and Ras mutant and a small molecule library to see what is common lethal between them and what is recessive lethal between the Ras mutant
-you want to screen for somthing that kills cancer cells but not normal cells

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7
Q

What are the 2 major types of cell immortilization?
What are the definitions of each?

A

-replicative senescene and crisis
-Replicative Senescence: an irreversible halt in cell proliferation with retention of cell viability over extended periods of time.
2. Crisis: “genetic catastrophe” that leads to death by apoptosis.

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8
Q

What is the difference between quiesence and senescense?
What do cells remain in senescense?
What is this often limit termed as, what does it mean?

A

quiesence=reversible and senescense=not reversible
-cells that remain metabolically active but have lost the ability to reenter cell cycle
-hayflick limit= the number of times a normal human cell population will divide until cell division stop

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9
Q

What are the various roads to senescence?

A

-

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10
Q

What does an oncogenic signal lead to?
What do Rb+p53 work to start?

A

-leads to downstream tumor suppressor breaks (rb+p53)
-they work to start senesence which is a cell arrest

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11
Q

What is sensecence triggered by?

A

-Senescence is triggered by telomere shortening, which can be bypassed by disruption of tumour suppressive (i.e.p53 and Rb) pathways

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12
Q

What happens after senecence bypasses?
What type of event is this?

A

after senescence bypass, cells undergo crisis, during which time chromosomes fuse leading to apoptosis (p53-independent).
Important: asynchronous event

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13
Q

What happens when there is unprotected chromatid ends?

A

-leads to end to end fusion

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14
Q

How do cancer cells escape crisis?
What happens to cells that have escaped crisis?

A

Cancer cells can escape crisis by expressing telomerase enzyme to keep long telomeres (85-90% of human tumors are telomerase positive)
-can then proliferate indefinitely and are therefore said to be immortalized

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15
Q

What is hypertrophy of cell?
When does this occur?
What are 2 examples?

A

-increase in cell size in reaction to a
physiological or pathological stimulus
-occurs in cells unable to divide.
* Ex. Skeletal muscle hypertrophy with training.
* Ex. Increase in cell size in cardiac muscle

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16
Q

What is hyperplasia?
When does it occur?
What are 2 examples?

A

-Hyperplasia: increase in cell number in response to a physiological or pathological stimuli, it is reversible
* Occurs in cells with a capacity to divide.
* Ex. Hyperplasia of epithelial cells in female breast during pregnancy.
* Ex. Liver regeneration

17
Q

What is neoplasia?
How does it arise?
What can neoplasias be?

A

-Neoplasm: new growth. A pathological disturbance of growth characterized by excessive and unceasing proliferation of cells, independent of normal regulatory controls and therefore is irreversible.
-Arise from genetic alterations.
-Neoplasms may be benign (not cancer) or malignant
(cancer)

18
Q

What is difference between hyperplasia and neoplasia?

A

-cells are genotypically and phenotypically normal.
* hyperplasia usually ends when the stimulus ends
(e.g. mammary epithelial hyperplasia). It’s reversible

19
Q

What is a benign tumor confined to?
What has a bening tumor not penetrated?

A

-a growth that is confined to a specific site within a tissue and gives no evidence of invading adjacent tissue.
-has not penetrated through the basement membrane

20
Q

What is the harm level of bening tumors?
What can some cause?

A

-Mostly are harmless; however, some can cause problems if they release high levels of hormones or are in specific locations (i.e. brain)

21
Q

What is a malignant tumor?
What are most cancer related deaths the result of?

A

-describing an aggressive growth that shows evidence of being
locally invasive and possibly even metastatic.
-90% of cancer-related deaths are the result of metastasis
spawned from original primary tumors

22
Q

What do we need in order to get a tumor that is 1cm in diamter?

A

-you need lots of doublinng in order to get a tumor that is 1cm diameter (1 billion cells)
-takes a while for tumor to grow

23
Q

How long cancers take to develop?
What is a key factor in cancer formation?
What cancer doesnt have good early detection methods?

A

-Most human cancers develop over many decades of time.
* age is a surprisingly large factor in the incidence of cancer
-pancreatic cancer

24
Q

Why does lung cancer related deaths have a slight delay compared to ciggarate smoking?

A

-there is a lag in the tumor being produced bc it takes many years

25
Q

Where is the cancer growth model well documented ?

A

Well-documented in the epithelia of the intestine (high rate of turnover)

26
Q

WHat underlies the epitelia of intestinal tract?
What is the epithelial layer the site for?
Where are cells rapidly dividing?

A

-Underlying these epithelia is a basement membrane (basal lamina) to which these cells are anchored.
-epithelial layer is the site of most of the pathological changes associated with the development of colon carcinomas
-in epithelial cells

27
Q

What do cells accumulate as tumor progression proceed?
What regulates cell proliferation?
In what stage can polyps be seen?
What is the early adenoma

A

genetic and epigenetic alterations
-APC (tumor suppressor gene)
-in the intermediate adenoma stage
-bening formation

28
Q

What gene inactivation leads to transition from late adenoma to carcinoma?

A

-inactivation of TP53 tumor suppresor gene

29
Q

What is carcinoma in situ?
What does it have the characterisitcs of?
But what are the 4 things that have not occured yet?

A

Is not a benign neoplasm but rather a carcinoma (stage 0)
-Has the biological genotype and phenotype of a malignancy, but…
* Has not invaded through the basement membrane.
* Cannot metastasize in it’s current state.
* Considered ‘pre-malignant’ or ’pre-cancerous’.
* As long as it’s completely removed/treated the patient will be cured.

30
Q

What does carcinoma in situ have the potential for?

A

-has potential to metastisize and become invasive because it has not yet passed the BM but can if left untreated

31
Q

What is EMT?
What is an important part of?

A

-it is the epithelial to mesenchymal transition
-wound repair and plays a role in cancer mutation/metastisis

32
Q

What occurs in the EMT process?
What do cells display

A

EMT is a cellular process during which epithelial cells acquire mesenchymal phenotypes and behaviour following the
downregulation of epithelial features.
* Cells display fibroblast-like morphology as well as increased migratory capacity

33
Q

What are the 4 core EMT (epithelial to mesenchymal transition) changes

A

Core EMT changes include:
1. Cytoskeletal remodeling.
2. Cell-cell adhesion weakening.
3. Acquisition of cell motility.
4. Basement membrane invasion.

34
Q

What is an intravasation?

A

-when mesenchymal cells enter the bloodstream

35
Q

What are the first 2 steps to invasion metastasis cascade?

A

1.Localized invasiveness enables in situ carcinoma cells to breach the basement membrane.
2. Intravasation into lymphatic or blood vessels.

36
Q

What are the last 2 steps for invasion metastasis cascade?

A

-3. Blood vessels can transport cancer cells to distant sites.
4. Cancer cells colonize to form metastatic tumors

37
Q

What is MET?
What do they acquire, reorganzie and exhibit?

A

MET (mesenchymal to epithelial transition).
* mesenchymal-like cells may acquire apical–basal polarity, reorganize their cytoskeleton, and exhibit increased cell–cell adhesion, resulting in an organized epithelium

38
Q

Where can cancers metastisize?

A

to many different locations