Fitz- Antineoplastics VI Flashcards Preview

IHO Week 4 > Fitz- Antineoplastics VI > Flashcards

Flashcards in Fitz- Antineoplastics VI Deck (38):
1

Must angiogenesis inhibitors work by decreasing substances that promote angiogenesis like:

VEGF
mTOR

2

What are the 3 things that mTOR does?

reduces cell growth/proliferation
prevent angiogenesis
increase the cytotoxicity of drugs that damage DNA

3

Thalomide is used to treat what two diseases?

Hansen's disease
multiple myeloma

4

What is the significant teratogenic effect of thalidomide?

phocomelia

5

What is the role of naturally occurring angiogenesis inhibitors in the growth of secondary tumors following surgery?

Some tumors secrete substances that inhibit angiogenesis at other tumor sites, so when a primary tumor is removed, some weeks later, metastases of the tumor can appear throughout the body.

*this indicates they were present all along but too small to be detected

6

What is rebound angiogenesis?

Rapid growth of cancer when an angiogenesis inhibitor is stopped

7

What drug acts on VEGF?

Bevacizumab

8

STIs (pazopanib, sorafenib, sunitinib) inhibit what two proteins?

VEGF-R
PDGF-R

9

What drugs inhibit FGF?

Thalidomide
Interferon

10

What drugs are mTOR inhibitors?

Everolimus
Temsirolilumus

11

What drug induces INFy?

IL-12--> increases inducible protein 10--> angiogenesis inhibtion

12

What drug decreases FGF production?

INF alpha

13

What is the role of VEGF-R in cancer?

VEGF-R is a tyrosine kinase receptor that activates mTOR in order to promote angiogenesis

14

What is mTOR and what does it do?

An intracellular serine/theronine kinase

Plays a central role in the control of cell growth and proliferation

Senses changes the availability of GFs/E sources and induces synthesis of proteins necessary for angiogenesis, cell growth/survival and nutriet uptake.

15

What proteins are regulated by mTOR?

Cell cycle regulators (cyclin D1)
AA and glucose transporters
proangiogenic factors
enzymes required for DNA repair

16

When is the mTOR pathway activated in cancer cells?

Uncontrolled proliferation

Increased mTOR in cancer cells--> secretion of VEGF and PDGF---> promote angiogenesis by increasing mTOR in vascular cells

17

What happens when you decrease the activity of VEGF-R and mTOR?

Synergistic kill of cancer cells

18

What is the MOA of bevacizumab?

Blocks VEGF

19

What are the SE of bevacizumab?

GI perforation
woud dehiscence
hemoptysis (spitting up blood)--> fatal

20

What drugs inhibit VEGF-R and PDGF-R?

Pazo and Suni- ckit
Sora- raf

21

What STI is associated with:
hepatotoxicity, hemorrhage, GI perforation and hypertension

Pazo

22

What STI is associated with:
hemorrhage, hypertension?

Sora

23

What STI is associated with:
hand-foot syndrome, skin discoloration?

Suni

24

What is the MOA of mTOR inhibitors?

1. Decrease cell growth and proliferation by blocking mTOR (decreasing bioenergetics)
2. Decrease VEGF and PDGF release from cancer cells
3. Increase cytotoxicity w/ drugs that damage DNA (damage w/ alkylating agent then mTOR force to continue cell cycle)

25

What are some of the toxicities associated w/ mTOR inhibitors?

hypersensitivity
immunosuppression
angioedema
kidney thrombosis
delays in wound healing
nephrotoxicity
male infertility
hyperlipidemia

26

What drug shifts the immune system from Th1--> Th2 and is a potent TNFalpha agent?

Thalidomide?

27

What are the SE of thalidomide?

Few in adult M and non-pregnant F

N/V, rashes, peripheral neuopathy, increased risk of DVT

28

What are the severe teratogenic effects of thalidomide if women take it 3-4 weeks post conception?

miscarriage
birth defects: malforned intestines, hearing defects, ocular/renal defects, phocomelia

*children and grand children affected
*single dose

29

What are the advantages of combination chemotherapy?

1. Synergistic effect: allowing you to decrease dose and therefore decrease toxicity to the pt

2. Decrease development of resistance--> decreased likelihood of clonal selection

3. Broader cell kill in cancers that consist of heterogenous tumor cell population

30

What strategies are used to select drugs for combination therapy?

1. effective alone
2. diff mechanism of action and diff mechanism of resistance
3. CCNS/CCS
4. Diff toxicities

31

What is pulse therapy? and why is it used?

Intermittent treatment w/ high doses of a drug, followed by free drug periods

Allows hematologic and immunologic recovery between treatment cycles

32

What is an example of pulse treatment?

MTX for the tx of choriocarcinoma

33

What is recruitment?

Use a CCNS drug to achieve a significant log kill

This causes cancer cells in Go to be recruited back into the cell cycle

THEN

You administer a CCS drug to kill dividing cells.

HUZZAH

34

What are examples of drugs used for recruitment?

CMF in breast cancer

DAUNOrubicin and cytarabine in AML

35

What is synchrony?

Use CCS drugs to synchronize cells into simultaneous cell division so that they're more sensitive to drugs/radiation.

36

What are examples of drugs used for synchrony?

Hydroxyurea followed by radiation

Vinca alkaloids followed by etoposide

MTX follwed by L asparaginase for ALL

37

What is rescue therapy?

Following the administration of toxic doses of a drug, normal cells are rescued by "antidotes" that ONLY they can use

38

What is an example of rescue therapy?

leucovorin following high dose of MTX