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BIOL311 > Cancer > Flashcards

Cancer Flashcards

1
Q

Number 1 Killers

A
  1. Heart Disease
  2. Cancer
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2
Q

Cancer

A

Unregulated cell division

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3
Q

How many types of cancer are there?

A

200 +/- types of histological cancers (types that we identify in a microscope)

***If we did further anlysis = we would get more in the group of 200

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4
Q

Problems/challenges in cancer

A
  1. Typical cancer has 5,000 mutations
  2. Only 5 driver mutations – challenger = to find the driver mutations and focus on them
  3. Fund function of driver mutations –> path to finding solution to cancer
  4. developing treatment modality
  5. Getting NIH funding
  6. Understanding the molecular basis of cancer
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5
Q

Mutations in cancer

A

Typical cancer has 5,000 mutations BUT only 5 driver mutations – the other 4,995 are passenger mutations

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6
Q

Driver mutation

A

Mutation that causes cancer

Challenge = find driver mutations and focus on them

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7
Q

Passenger mutations

A

Mutations that are NOT the dirver mutations – the other 4,995 mutations that do not cause cancer

***They ride along – don’t cause cancer

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8
Q

Path to finding solution for cancer

A

Finding the driver mutations

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9
Q

Best form of cancer treatment

A

Modality if done in the besty way has to selecivley target cancer cells and not bother the neighboring cells

***Most cancer treatments today still bother neighboring cells

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10
Q

NIH funding

A

Invest billions of dollars to target cancer –> mostly through their cancer institute

***There are many people working on cancer = hard to get money

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11
Q

Understanding the molecular basis of cancer (Ex.)

A

Example - understanding what driver mutations do

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12
Q

Understanding the molecular basis of cancer + Cure

A

Understanding the molecular basis of cancer does not equal a cure right away –> takes time to design drugs to treat cancer

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13
Q

Tradition vs. New era cancer treatments

A

Traditional – out for a while but is not cancer cell specific

New era – More specific drug –> use immunotherapy (Car-T-Cells)
- Based on driver mutations

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14
Q

Why compare cancer vs. Normal cells

A

Comparing the two gives us tools to make drugs

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15
Q

Cancer cell characteristics

A

Not all cancer cells fit into all compartments –> need to do many tests to test for cancer

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16
Q

Normal Vs. Cancer cells

A
  1. Soft Agar growth
  2. Keryotype
  3. miRNA
  4. Protease sectretion
  5. Size
  6. Nucleus/Cytoplasm ratio
  7. Cytoskleton
  8. ECM
  9. Growth Layers
  10. SCID mouse
  11. Serum dependencey
  12. Growth factor secretion
  13. telemors length
  14. Gentic defects
  15. Glycolysis
  16. Cell memebrane permeability
  17. Angrogenic factor secretion
  18. Apoptosis
  19. RTKs
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17
Q

Normal vs. cancer soft agar growth

A

Normal – do not grow in soft agar (do not grow in semi-solid media)

Cancer – Grow in semi solid media (cells grow + divide + make clones)

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18
Q

Semi-solid media

A

Soft Agar

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19
Q

Why don’t normal cells grow in Soft agar

A

Normal cells = substarte dependt cells –> they die because they are substarte dependnet (agar doesn’t let them bind to other things = they die)

***The cancer = not substrate dependent = don’t need to stick to a surface = gorw in semi-solid media

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20
Q

Clones in Cancer cell media

A

You can pick a clone and look at its behavior –> can fine a cancer stem cell that gave rise to the tumor

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21
Q

Normal vs. Cancer Keryotype

A

Normal – have typical karyotype (have all 23 sets of chromsomes)

Cancer – Atypical Karyotype –> might have 3 copies of chromosomes (like chromoses when making hybridioma – where they are not normal)

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22
Q

Normal vs. Cancer miRNA

A

Normal cells – Normal set of miRNA

Cancer cells – abnormal set of miRNA –> miRNA based on quality of cancer (not being used in technology to make drigs)

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23
Q

Normal vs. Cancer Proteases

A

Normal cells – secrete few proteases – all cells secrete proteases

Cancer cells – Typically has lots of proteases
***Makes cancer metastatic

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24
Q

Cancer cell secretion

A

Secretes colleganse + proteases –> done to walk on EC< + allows them to metastsize

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25
Q

Normal vs. Cancer size

A

Normal cells – usually larger (usually found in G0)

Cancer cells – Usullay smaller – usually going through cell cyle = going through mitosis = smaller

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26
Q

Normal vs. Cancer cytoplasmic ratio

A

Normal cells– Lower nucleus to cytoplasm ration

Cancer cells – Higher nuclues to cytoplasm ratio

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27
Q

Normal vs. Cancer cytosleloton

A

Normal cells – Cytoskeleton is organized

Cancer cells – Cytoskeleton is less organized

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28
Q

Normal vs. Cancer ECM

A

Normal cells – Exctensive ECM

Cancer cells – Low ECM (Have no firbrnotectin because it would make it get stuck and it wants to move)

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29
Q

Normal vs. Cancer layer growth

A

Normal cells – Grow in a single layer

Cancer cells – Grow in culture in multilayer (they have no contact inhibition = they don’t stop dividing)

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30
Q

Why do normal cells grow in one layer

A

Because normal cells are characterized by contact inhibition – once it is multilayer = the cells are in contact = they stop dividing

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31
Q

Normal vs. Cancer SCID mouse

A

Normal cells – No tumors in SCID mouse

Cancer cells – Generate tumors in SCID mouse –> used to test if you have cancer cells that generate a tumor

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32
Q

Normal vs. Cancer Serum need

A

Normal cells – serum dependent growth (need fetal calf serum)

Cancer cells – Don’t always require serum (depends on the cancer cell) –> some cancer is very clever

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33
Q

Normal vs. Cancer Growth factors

A

Normal cells– secrete few growth factors (unless they are designed to do that)

Cancer cells – Secrete their own Growth factors (Autocrine)

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34
Q

What cell secrete growth factors

A
  1. cancer cells
  2. normal cells in the hypothalamus – designed to secrete growth factors
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35
Q

Normal vs. Cancer telemeres

A

Normal cells – telemeres shortes every cell division

Cancer cells – telemeres never shorten (requirment for cancer)

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36
Q

Prerequistite for cancer

A

Long telemers – require that the telemeres never shorten

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37
Q

Telemer size

A

Somocent cells (few divisons = short telemers) –> Somatic cells (25-50 disvison – depends on teh age of the donor) –> Adult Stem cells (100-200) –> Cancer cells (immortal)

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38
Q

Cancer cell mortality

A

Cancer cells = immortal even though on occasion a few will go through apoptosis

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39
Q

Normal vs. Cancer genetic defects

A

Normal cells – few genetic defects

Cancer cells – Lots of mutations

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40
Q

Normal vs. Cancer Glycolysis

A

Normal cells – normal glycolysis

Cancer cells – warburg effect

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41
Q

Normal vs. Cancer cell memebrane

A

Normal cells – normal outter CM permeability

Cancer cells – higher permability of Cell memebrane (10X permeablity)

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42
Q

Normal vs. Cancer androgenic factors

A

Normal cells – don’t secrete andorgenic factors

Cancer cells – Solid tumors (some cancers) secrete androgenic factors

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43
Q

Example Androgenic factor

A

Ex. VEGF

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44
Q

Why are tumors white

A

Because they have few blood vessels

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45
Q

Normal vs. Cancer Apoptosis

A

Normal cells – normal apoptosis

Cancer cells – can resist apoptosis –> can happen in many ways (ex. Virus)

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46
Q

Normal vs. Cancer RTKs

A

Normal cells – RTKs – receteprots that are stimulated by hormes/growth factors that cause cell to divise (normal = normal RTKs)

Cancer cells – defective RTKs (mutated) –> constitutive = not regulates (always turned on)

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47
Q

FDA + cancer drugs

A

DATELINE – FDA steps up to the plate

  • FDA = issued warning letters to 14 companies for marketing supplements that can cure cancer but do not have a proven + documentable outcome

***65 products total

Suplement = not FDA apporved

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48
Q

Model organism for studying cancer

A

Zebra fish – used to study defective genes that cause melanoma

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49
Q

Ocular melanoma story

A

Ocular melanoma = 6/1 million BUT 4 friends in Auburn all have it

***Don’t know why they all have it

Example of time when there is a cluster of cancer –> more people have cancer than you would expect

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50
Q

General progression of cancer

A
  1. Intitaion (mutation event in somatic cell)
  2. Cancer progression (mutauin and genome detsabilization + dysregulation of growth control pathways)
    • Have proliferating cells (takes time to make a tumor)
  3. Evasion of cancer elimination (Block apoptosis + blocj Killing by T-cells) –> Precacerous cells
    • Apoptosis normally occurs because of tumor supressor genes BUT in cancer progression the cancer blocks the apoptosis
    • Blocking T-cells = basis of immunotherapy –> because canver have receptors that say “don’t kill me” = the T-cells can’t kill it
  4. Tumor growth + dispersion
    • Tumor can release factors to grow blood vessels
      - Have angiogenisis (grow blood vessles) + metastsasis
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51
Q

Example precacerous cell

A

Colon polyp

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52
Q

Gardasil

A

First cancer vaccine – now can be used for both boys and girls to prevent up to 90% HPV infections that can cause cervical and other cancers

***They wanted the HPV vaccine to be required for girls going into highschool – very controvrsial

Texas: Former Gov. Rick Perry ( US Energy Secretary 2017 - 2019) mandated vaccination in 2007 (Merck donated $$ to his campaign) for girls and then reversed position due to public opposition

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53
Q

HPV

A

STD

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54
Q

What causes cancer

A

MANY THINGS can cause cancer
1. Viruses
2. Radiation (UV light)
3. Chemical Mutangens
4. Blocking CDks/cylins
5. Defective tumor supressor genes
6. Defective DNA correction.DNA repair enzymes
7. Defects in apoptosis pathway
8. Defects on growth factor signalling path
9. Telemers
10. Cancer stem cells
11. Chromosmal translocation
12. DBA amplification
13. Overproducting and or mutating trasncription factors

***Once find out what causes cancer = can find treatments

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55
Q

Viruses that cause cancer

A
  1. Sacrcoma Virus
  2. SV40
  3. HPV
  4. Epstein Barr Virus
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56
Q

History Sarcoma Virus

A

Reserachers found that virus caused cancer in 1911

1911 – reserachers = figured out that virsues can cause cancer using the Rous Sarcoma Virus (Rouse sarcoma = showed that viruses can cause cancer)

1970 – they still thought the basis of cancer was virsuses –> could not sequence things

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57
Q

Result of sequencing the Rouse Sarcoma Virus

A
  1. Found V-SRC – Rouse Sarcoma Virus
  2. Found V-SRC is similar to C-SRC
    • C-SRC = protooncogene (normal gene)
      - C-SRC is found in Us

Virus = takes C-SRC and turns it into V-SRC –> turns it into a cancer gene

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58
Q

SV40

A

Virus that can cause cancer
***Has large T-antigen

Once it gets into cells it knows it needs to take out tumor supressor genes

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59
Q

SV40 T Antigen

A

Has to sites

Site #1 – for p53 gene
Site #2 – for R3 gene

Once it gets into cell it knows it needs to take out tumor supressor genes –> large T antigen takes out the tumor supressor genes

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60
Q

HPV

A

Human Pavlova Virus – virus that can cause cancer

***Causes cirvical carcinoma (HeLa cells)
- Gardasil = 1st cancer vaccine

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61
Q

First cancer vaccine

A

Gardasil – for HPV -> revolutionized how we think about treating cancer

62
Q

Epsetin Varr virus

A

Virus that causes cancer –> causing Hotchikning Lymphoma

***Causes translocation of chromsomes

63
Q

Paradox on radiation/UV light

A

Paradox = radiation causes skin cancer BUt radiation is a common way to treat tumors

64
Q

Affect of UV light

A

Causes thiamine dimers –> usually you have repair enzymes that fix it

65
Q

Types of chemical mutungens

A
  1. Direct
  2. Indirect

***Most chemical mutagens = known

66
Q

Tobacco smoke

A

Type of chemical mutagen – includes promoters + initiators

***Have both types of mutagens

67
Q

Blocking g1

A

Can block g1 by blocking cylcin + CDK

**Defective cyclins = often found in cancer
**Checkpoint doesn’t work

Example – breast cancer – many breast cancers = have defective cyclin D = p53 won’t stop things

***p53 and other checkpint controls work by inhibiting cyclin-CDKs – if p53 doesnt work than cancer can result

68
Q

Defective tumor supressor genes Ex

A

Example – p53 –> we know that over 50% of cancer have defective p53 + defective RAS

69
Q

Defective DNA correction ex.

A

We know that defective DNA correction/DNA repair enzymes cause many cancers

Example cancer = Xeroderma Pigmentosa

70
Q

Defects in apoptosis pathway Examples

A

Examples:
1. defective p53 –> because p53 causes apoptosis
2. Bcl2 –> if high Bcl2 = chemo and radaition won’t work because Bcl2 is an anti-apoptic protein

71
Q

Defects in growth factor signalling path

A

Very variable

Example:
1. RTK path – because RTKs = signla cell to divide
2. TGF Beta –> affects growth receptors – interacts with receptors and stops cell division = if it is defcetive them you get cell division

72
Q

Fewest number of cell divisions

A

Have the fewest number of cell divsions in aging cells

73
Q

Telemers + cancer

A

Inability to shorten telemers = causes cancer

Cancer = repairs telemers + keeps them long

74
Q

Cancer stem cells

A

May be the major of cancer –> they may give rise to mature cancer cells

- They were orginally rejected --> made us rethink how we think of cancer developmnet 
 - May be responsible for metastasis
 - Often reisistent to standrad chemo = they are a big challenge
75
Q

Amount of cancer stem cells

A

There are very few of them –> less than 10% of tumor = they are hard to find

76
Q

Finding cancer stem cells

A

They are hard to find because there are so few BUT then we started cloning cells and found that one cancer stem cell acts different than the other clones

77
Q

Surface marker of cancer stem cells

A

CD133 – CD133 positive cells = likley a cancer stem cell

***You can use FACS and purify cancer stem cells using the surface marker CD133

78
Q

Example chromosmal translocation

A

Barkitts lymphoma

79
Q

Example DNA amplification

A

Amplifying genes for growth factors –> causes cancer

80
Q

Overproducing or mutations in transcription factors

A

Example:
1. FOS –> early response gene
2. MYC –> Late response gene

***Both important in G1 cell cycle (both are early and late response genes in G1)

81
Q

NY + HPV

A

NY bill would require HPV vaccine for children to enter school, daycare. As of 5/21 - Only four jurisdictions currently require HPV vaccine for school entry: Rhode Island, Virginia, Puerto Rico, and the District of Columbia (DC).

NY = trying to have law that you need HPV vaccine for preschoolers (vaccine = gardacil)

82
Q

p35 process

A

DNA damage –> ATM/R –> Phosphorylates p53 = p53 active –> p53 affects G1 CDKs

83
Q

Example cancer stem cells

A

Chronic Myelogenous Luekemia – they are rageting it with HDAC inhibitors

Treatment –
Just Imatinib –> Use Imatinib kills tumor but when stop the tumor keeps growing – keeps growing because cancer stem cells generate more tumor

 - means you need two drugs to also kill cancer stem cells in order to find cure

Imatinib + HDAC –> using two drugs to kill cancer stem cells + the tumor cells

84
Q

Imatinib

A

Kills tumor BUT not cancer stem cells

ALSO used to block BCR – made knowinh the substarte = blocks ability of chromosome to phosphorykate substrate = no cell division
(Imatnib = binds to actuve site and inhibits subsrate binding)

85
Q

BCR-ABls Protein kinase

A

Results in “philideplphia” Chrmosome

***In luekemia = have translocationon philedelphia chromsome –> have fusion of gene – makes Bcr able to fuse genes –> protein phosphorylates substarte = cell survives = cell is a cancer cell

Have translocation = fusion of genes = gets transcribed and makes the BCR-fusiogenic protein –> protein gets phosphorylated (protein = substarte) –> phosphorylation = canuses cell division = cell is cancer cell

86
Q

Example Oncogene

A

V-SARC - oncogene

87
Q

Classic Oncogene experiment

A

Focus = on oncogenes

Experiment #1:
Took DNA from human tumor –> isolated DNA –> Put DNA into 3T3 cells –> get cancer cell

Result: get clones – clones = cancer cells
***The clones were multilayer in contact with each other = know they are cancer cells

Experiment #2:
Realized that 1 oncogene doesn’t necessarily transform all cells
Part 1 – Take 3T3 cells + DNA with oncogene (add haRAS oncogene)
Result: Get cancer

Part 2 – Take REF cell (rat embryo fibroblast) –> Add DNA with oncogene (add haRAS oncogene)
Result: No cancer
BUT then took the trasnfected REF cell and but in a new microenvirnment (put in semi-solid media)
Result: Got a cancer cell

Experiment = suggested that can cells care about their microenvirnment + showed that 1 oncogene doesn’t necessarily trasnform all cells

88
Q

Robert Weinberg

A

Worked on oncogenes

***Isolated the 1st tumor supressor gene Rb + showed oncogenes are not specifc specific

***Was one of the founders of the cancer institute at Harvard

***He started Vera Stem –> Biotech company for cancer – focuses on his second discovery (RAS causing cancer)

89
Q

What did Robert Weinberg Discover

A
  1. Discovered the 1st tumor supressor gene –> found Rethoblastoma gene (Rb gene)
  2. Discoveres RAS oncogene –> found RAS deviant that causes cancer
90
Q

Oncogene

A

Causes cancer – usually needs to have other oncogenes with it to be able to cause cancer

91
Q

Protooncogene

A

Normal gene that typically are related to cell division pathways

92
Q

Age + cancer

A

Cancer= age dependent – we know that most but not all cancers take time to develop –> increase with age

***Older = more likley to get cancer

93
Q

Multiple hit model of cancer

A

**Known for a while
**Typically need multiple oncogenes to cause cabcer

  1. Know most but not all cancers take time to develope –> reason why cancer increases with age
  2. Know most cancers = caused by epithelial cells
94
Q

Multiple hit model of cancer

A

**Known for a while
**Typically need multiple oncogenes to cause cancer

  1. Know most but not all cancers take time to develop –> reason why cancer increases with age
  2. Know most cancers = caused by epithelial cells
95
Q

Experiment for multi-hit model of cancer

A

Look at tumor incidince in 3 mice
- Over time the percent of tumor free mice

Use three transgenic mice: have mutations in genes that increase cancer
1. MYC mouse
2. RAS mouse
3. MYC + RAS Mouse

Result: Over time the amount of tumor free mice decrease – mice with most tumors = older mouse with mutations in both genes

Shows cancer = increases over time + often need multiple oncogenes to cause cancer

96
Q

Clinical Application of Multi-hit cancer

A

Colon cancer

97
Q

Colon cancer

A

Colon cancer = very slow growing cancer –> easy to prevent

- Have defects that occur sequentially until you get to a point of no return (once its metastisized you can't help) BUT it takes many yeats to get there = you can taje out the polyps before that happens and it won't metastisize = reason why get colonoscopy because you can take out the polyps (because it takes a while for the polyps to be able to metastisize)

50% of people have poplys – precancerous

Cancer = Can be prevented by having a colonoscopy

98
Q

Do tumors orginate from a single cell or many cells

A

Answer: Comes from a single cell

How do we know:
Women = a mosaic of cells

If look at tumors in women –> You always have the same X chromsome activated in teh tumor cells as the X chromsome activated in teh cell it orginated from

Women = verified the fact that tumors come from one single cell

99
Q

Tissues in women

A

Women = mosiac of cells –> because the tissues in female only have one X chromsome that is activated

100
Q

Oncogenes + RTKs

A

Many oncogenes aere associated with RTKs

Example:
Have HER2 receptor – protooncogene + EGF recepor (EGF = inactive)

THEN have single change in one Amino Acid

HER2 –> NEU oncoprotein – NOW always on

OR have a delation
EGF –> ERbB oncoprotein – always on = constitutive

101
Q

Chimeric Oncoproteins

A

A few oncoproteins are chimeras

Ex. Chimeric Trk oncoprotein – C termical of Tropomysoin binds to Trk receptor = get cancer

102
Q

SFFV

A

Some oncogenes are due to interactions with Virus Glycoproteins – SFFC (Spleen focus forming virus) = example –> results in excessive number RBCs

How does it work:
A 55,000 da glycoprotein from virus binds to Epo RTK = turns it on –> get RBCs (have hematoposis)

Causes – Eurothro Lukemia – overproduction of RBCs

103
Q

1st tumpr supresser gene discovered

A

Rb - Retenoblastomal

***Discovered by Robert Weinburg

104
Q

Rb (retinoblastoma)

A

Tumor supresser gene

Comes from nueronal stem cells
***Bilateral –> affects retina –> Kids can go blind

1/200,000

***to treat = use enuculation –> take eye out

105
Q

How can you get Rb

A

Can be inherited or sparatic
- Inherited dfective gene – inherit one loss of function alele (have normal cell because receisisve) BUT then have another loss of function mutations – homozygous loss of function (because now both have loss of function allele) cell gives rise to tumors in retina
- Sparatic – have loss of functional gene – need 2 sparatic mutations to occur = rare
- Sparatic = inherit two healthy alleles –> have one loss of function mutaion THEN anoteh rloss of function mutation and teh homozygous loss of function gives rise to tumor
***can occur from missegragation during mitosis

106
Q

Tumor Supressor Genes (list)

A
  1. P53
  2. Rb
  3. BRACA 1/2
    4.
107
Q

3rd way to get mutated Rb

A

Misegrigation + recombination – if have 1 defcetive allele through misegregation then have recombination

108
Q

Defect in p53

A

Results in Li Frimueni Syndrome –> have 25X higher chance of getting cancer

109
Q

BRACA 1/2

A

Tumor supressor gene – normal function is repair DNA breaks

Defective gene = increases breast cancer (60% chance of getting breastcancer VS normal chance without mutation is 2%)
**Some people with mutatations have masectamy before the cancer developes
**There was a law suit based on BRACA assay

110
Q

Genetic Tests

A

There are 1300 gentic tests for human diseases including cancer suceptability such as BRACA

***There was a big lawsuit based on BRACA assay

111
Q

Types of Carginagens

A

Indirect –> the native form does not cause cancer BUT when they are processed by the liver Cytp450 takes the indirect and makes it into a carcinogen (because the cytp450 cant tell a difference between the indirect and not harmful things)

Direct –> Does soemthing to DNA to a point where p53 can’t correct it

112
Q

Example Indirect Carcinogen

A
  1. Aflotoxin (peanut fungus that mutates p53)
  2. Benzo pyerene
113
Q

DNA repair

A

Tumor supressir genes look for and repair mistakes in DNA

114
Q

DNA repair enzymes

A

We have DNA repair enzymes that fix defective genes

115
Q

Xerdoma Pigmentosa

A

Inherited disease that is caused by probelms with DNA repair enzymes

  • Affects kids
  • Charcahterized by many skin lesions because of UV sensityity –> can’t repair thiamine dimers

***Camp sundown = camo for kids with UV sensitivity disorder + midnight sun is a movie based on story of person with XP

116
Q

Liquid biopsy

A

Used to detect cancer – we now have liquid biopsy that is a real way to detect cancer

Galeri Test – idetifies cancer by looking at cfDNA – can idetify 50+ types of cancer
- Many peolpe investing
- Recomended for adults with risk of cancer – not replacing other cancer screening methods

117
Q

Cancer treatment catagories

A
  1. Radiation
  2. Surgical Ablation (Resection)
  3. Chemothearapy using non-biologics (drugs)
  4. Biologics (mABs + conjugated antobodies)
  5. Immunotherapy
118
Q

What is part of radiation

A
  1. Brachythearpy – injecting radioisotope into tumor (radioactive seeds) –> localized – good for solid tumors
  2. EBRT (External Beam Radiation Thearapy) – Cyberknife – no seeds + focuses on tumor
119
Q

How does radiation work

A

Overall: Works by triggering checkpoint systems resulting in apoptosis

***Causes so many issues in target tissue then p53 will come in and cause apoptosis
- Bad if p53 is defective – then you are just making cancer

120
Q

Da vinci system

A

Robotic system for prostate cancer – Surgical!!!

Example of surgical ablation – remove the cancer

121
Q

Systems for surgical Ablation

A
  1. Da vinci System (prostate cancer)
  2. SCN PSN systems – cryoablation

Surgery = removing the cancer

122
Q

SCN + PSN Systems

A

Surgical option – treats cancers with cryoablation
- Uses slender catheter to then reach and kill cancer –> kill cancer with heat + cold

***Used for prostate cancer – made a prostate cancer tissue to test it on using tissue engineering

123
Q

Taxol

A

Chemo Drug
Targets the M phase – promotes polymerizes = interferes with spindle

124
Q

Taxol Vs. Taxotrene

A

taxol = natural product

Taxatrene = semi synthetic – taxol is hard to harvest enough from trees = made synthetic product

***Both = target microtubulues

***Clinical name = pacitaxel

125
Q

M phase checkpoint

A

Looks at microtubulues –> sees if there are mistakes – if there are mistakes then it triggers apoptosis

Taxol = affects the spindle = affects the M phase checkpoint

126
Q

5-Flourouracil

A

Chemo drug – Drug that looks like a DNA based but isn’t –> Cell incorportaes it into DNA –> p53 sees it and can’t fix the probelm so it makes teh cell go through apoptosis

**Triggers DNA damage
**Most common chemo drug
***Affects RNA + DNA

127
Q

Imatinib

A

Chemo drug – Inhibits the bcr-abl fusion protein

***Designed based on BCR able protein –> protein kinase – inhibits BCR kinase = no phosphorylation = no cancer

***Needed to know molceular action in order to make drug

128
Q

Tamoxifen

A

Chemo Drug – Competative antagonist of estrogen receptor

***Used with women worried about breast cancer

129
Q

Biologics

A

Includes:
1. mAB
2. Conjugated antibodies – synthetic bispecific AB

***Billion dollar industry

130
Q

Bispecific Antibody

A

Has two different FaB regions = one binds to cancer cell and one binds to T-cell –> brings the two together = kill cancer cell

Trifunctional
Generated using quodroma cell lines – two different FaB ends

Ex. Catumaxomab

131
Q

mAB list

A
  1. Herceptin
  2. Kadcyla
  3. L-DOS 47
132
Q

Herceptin

A

mAB used for breast cancer
- Used for HER2 positive breast cancer –> 1-2 million HER2 receptors

How does it work:
HER2 = RTK –> causes cell division BUT with teh AB the AB blocks dimerizations = can’t bind HER2 to ligand = no cell division

133
Q

1st mAB used for cancer

A

Herceptin (1998)

134
Q

HER2

A

Alone = not an oncoprotein BUT overproduction of HER2 (overexpression) = leads to cancer –> have more cell division

135
Q

Kadcyla

A

Conjugated mAB – 2nd generation HER2

***Has DM1 attatched –> DM1 affects microtubulues = triggers Mphase checkpoint

How does it work:
Cell endocytoses the DM1 + AB blocks HER2 receptor –> HAS TWO EFFECTS

136
Q

L-DOS 47

A

Conjugated AB BUT has nothing bound to it INSTEAD it has Urease

Urease – binds to cell = changes teh pH (increase pH) around the cancer cell = kills it

***Changes the microenvirnment = kills cancer

***Acidic envirnment prevents T-cell attacks of tumor cells = it makes envirnment less acidic

***In clincal trials

137
Q

Avastin

A

Blocks angiogensis – many solid tumors secrete angiogensis factors = blood vessls grow towards the tumor

Avastin acts like sponge – binds to VEGF surrounding the tumor

138
Q

2nd Use of Avastin

A

Used to treat macular degeneration

139
Q

Combination Thearpy

A

Overall: treating cancer = use many things in cocktail –> drugs are not used in isolation – they are used in combination to target different forms of the cell

R-CHOP – mAB

140
Q

Immune system + Cancer

A

Immune system = can recognize solid tumors and approach

Issue: Tumor cells = have a don’t kill me sign

141
Q

History of Immunothearapy

A

Start = Dedreon –> They thought to built a better immune system to attack cancer cell better –> they took a dendritic cell and genetically modified it so that they are more robust so they could kill cancer

Dedreon target = prostate cancer

Results: It works –> gave people 4 more months to live but insurance companies did not want to help people pay for it = the company went out of buissness

Begining of interest in immunotheraoy – dedreaon treating prostate cancer

142
Q

Immunothearapies

A

Treatment regime that directs an individual’s immune system to fight cancer by either stimulating it to attcak cancer cells or by introducing manufactured immune system componenents top augment immune function

KEY = T-cells recignize and eradicate cancer cells

143
Q

CAR-T cells

A

T-cells with CAR modification –> Take out T cells and modify them so that they now express CAR receptor –> Now its AB like molecule –> CAR-T cells can bind to the target cancer lymphoma cells = can kill the cancer cells

CAR = Chimeric Antigen receptor

***Genetically modified T cell

144
Q

Approaches of immunotherapy

A
  1. Stimulate iverall immune system response of patients
  2. Introduce engineered T cells harvest from pateints with CAR modified T cells
145
Q

When can you use Immunothearpy CAR-T Cells

A

Doesn’t work in solid tumors – works in liquid tumors

146
Q

History of CAR-T Cells

A

First used with Chronic Lymphatic Leukemia (CLL)

147
Q

Immunotherapies challenges

A
  1. Tumor cells can express multiple inhibitory ligans to repress T-cell function and thereby evade being targeted by the immune system
  2. Challenges is to design a CAR -T cell that targets only the target tumor and not similar surroudning tissue
  3. Sever toxicty can occur leading to death
  4. Not currentley applicable for solid non-blood tumors (like liver tumors)
148
Q

Keytruda

A

Immunithearpy that blocks the “don’t kill me signal” on tumor cells

Anti-PDL – ant-PD1 mABs FDA approved

mAB – blocks PD-L!

Some blocks PD-L1 some blocks PD1

149
Q

Future of cancer things

A

Wearable CTC Filter system

Device = collects and counts CTCs – monotiors tumor load = know if you need to go back/change chemo treatment

***Shows if chemo works

Second thing = finding and understanding driver mutations –> make drugs

150
Q

Holy grail of cancer drugs

A

Selectively kill cancer cells

BIOL311 (4 decks)

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