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Pharm Spring 2014 > Chemotherapy > Flashcards

Flashcards in Chemotherapy Deck (51)
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1

What type of therapies is cancer treatment moving towards?

Targeted therapies

2

How is cancer categorized?

By origin and mutational status

3

What is the 2 part definition of cancer?

Cells that divide uncontrollable and can invade nearby tissues

4

Sarcomas affect what tissues?

Fat, bone, muscle

5

What are the 6 hallmarks of cancer?

Limitless replication, evading apoptosis, self-sifficient growth hormone production, insensitivity to anti-growth signals, angiogenesis, and tissues invasion/metastasis

6

In what way are cancer cells able to avoid apoptosis?

Normally, damage to DNA will cause the cell to undergo apoptosis. In cancer cells, many mutations exist, including those to allow it to avoid apoptosis and to grow more rapidly.

7

How are cancer cells able to invade and metastasize?

Because of the other properties of cancer cells (self-sufficiency of growth hormones and loss of contact inhibition). Normally, healthy cells rely on neighboring cells for signals to grow and stop growing, however, cancer is able to survive on it's own as long as it has a blood supply.

8

How are cancer cells able to replicate without limit?

Active telomerase. In healthy cells, telomerase is usually inactive. In cancer cells, telomerase is actively lengthening telomeres, rendering the cell immortal. This makes the cell more prone to mutations and more prone to pass those mutations on to daughter cells.

9

In normal cells, shortening of the telomere causes the cell to enter this state

Replicative senescence

10

Are tumor suppressor genes dominant or recessive?

Recessive. Tumor suppressor genes generally follow the "two-hit hypothesis," which implies that both alleles that code for a particular protein must be affected before an effect is manifested. This is because if only one allele for the gene is damaged, the second can still produce the correct protein. In other words, mutant tumor suppressors' alleles are usually recessive whereas mutant oncogene alleles are typically dominant.

11

Give an example of a tumor suppressor gene

p53

12

What is the role of p53?

p53 prevents cells with damaged DNA from proliferating. It is known as the "guardian of the genome." About 50% of people with cancer have a mutate p53 gene.

13

How does p53 work?

Certain damage to the DNA will cause p53 to activate. There is a checkpoint between the G1 and S (synthesis) phases, where p53 will be activated if need be. p53 will then decide if the damage is repairable or irreparable. If repairable, the cell goes into cell cycle arrest, during which DNA repair occurs. If irreparable, p53 activates apoptosis.

14

Are you able to inherit somatic mutations?

No.

15

What is Li-Fraumeni Syndrome?

A germline mutation of the p53 gene. People with this mutation are about 25x more likely to have cancer by age 50, and are more likely to get cancer at an early age.

16

Are germline mutations found in all of your cells?

Yes.

17

What is the typical signal transduction cascade leading to DNA transcription and proliferation?

RAS -> RAF -> MEK-> ERK

ERK then enters the nucleus to stimulate transcription factors.

18

Are RAS, RAF, MEK, and ERK tumor suppressor genes or proto-oncogenes?

Proto-oncogenes

19

Are proto-oncogenes dominant or recessive?

Dominant

20

What is an oncogene?

A proto-oncogene that has undergone a mutation

21

What do oncogenes cause?

Altered cellular functions that can lead to spontaneous, abnormal growth.

22

What are some general examples of proto-oncogenes?

Growth factors, growth factor receptors, and signal transduction proteins.

23

What types of things can cause mutations to proto-oncogenes?

Mutagens, carcinogens, radiation, viruses, and genetic predisposition.

24

What are the three main goals of chemo?

1) Inhibit DNA synthesis to prevent mitosis (methotrexate)
2) Damage the DNA of cancer cells (alkylating agent)
3) Stop mitosis and therefore, cellular division

25

Most chemo drugs are non-specific and can lead to

Toxicity

26

How does methotrexate work?

Methotrexate has a higher affinity for DHFR than FH2 does. This reduces the amount of FH4 and subsequently the amount of thymidine available for DNA production.

27

How do cytotoxic antibiotics work?

By interfering with DNA replication and transcription

28

Give 1 example of a cytotoxic antibiotic

Doxorubicin

29

How does doxorubicin work?

By inhibiting topoisomerase II. Normally topoisomerase II will break the DNA, unwind it, and then reseal it. In this case, the topoisomerase breaks the DNA, doxorubicin binds to the DNA, and topoisomerase II is unable to close the DNA back together.

30

How do alkylating agents work?

By directly damaging DNA. Alkylating agents attach alkyl groups to the guanine bases of DNA. This causes intra and inter-strand linking to occur, blocking the activity of DNA polymerase.

31

Give one example of an alkylating agent

Cyclophosphamide.

32

How do vinca alkaloids work?

By preventing of tubulin from forming into microtubules. That means there are no microtubules around to form spindles. This prevents sister chromatids from being pulled apart, preventing mitosis.

33

Give one example of a vinca alkyloid

Vincristine

34

3 Types of targeted therapies discussed in class

1) Hormone therapy
2) Monoclonal antibodies
3) Tyrosine kinase inhibitors

35

How does tamoxifen work?

It binds to estrogen receptors, but without causing a conformational change in the receptor. Without this change, co-activators cannot bind to the receptor to result in translation and transcription of proteins. This drug specifically stops breast cancer that requires estrogen to grow.

36

What is unique about tamoxifen?

The medication itself is not active. It's metabolite is.

37

How do monoclonal antibodies work?

1) Blocking growth signals
2) Preventing angiogenesis

38

Monoclonal antibodies usually end in this suffix

mab

39

Give one example of a monoclonal antibody that blocks growth signals

Cetuximab

40

How does cetuximab work?

Blocks EGFRs (epiderminal growth factor receptors), preventing the normal kinase cascade from occurring (RAS, RAF, MEK, ERK)

41

Give one example of a monoclonal antibody that works by preventing angiogenesis

Bevacuzimab

42

How does bevacuzimab work?

By binding to VEGF (vascular endothelial growth factor). This way, VEGF is unable to bind do its receptor, preventing cross-phosphorylation that leads to a transduction cascade ending in angiogenesis.

43

BRAF is mutated is ___% of melanomas and the ______ mutation makes up 60% of BRAF mutations

80%
V600E

44

What happens as the result of a V600E mutation?

It means that at amino acid 600, valine is mutated to a glutamic acid. Because of this, the BRAF protein is always active causing cellular proliferation.

45

How does Vemurafenib work?

It ONLY inhibits the V600E mutated form of BRAF.

46

Vemurafenib is also known as

PLX4032

47

The philadelphia chromosome can be seen in this type of cancer

Myelogenous leukemia

48

What is the philadelphic chromosome and why is it bad?

Swapping of chromosomes 9 and 22 lead to ABL and BRC being on the same chromosome. The BRC-ABL protein is a tyrosine kinase that is always active, that leads to activation of multiple pathways that lead to cell proliferation and cancer.

49

How does Gleevec (Imatinib) work?

Binds to the ATP binding site of the BRC-ABL protein, which inhibits its kinase activity.

50

Tyrosine kinase inhibitors end in

ib

51

What do proto-oncogenes normally do?

Stimulate cellular proliferation