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Flashcards in Cancer (objectives only) Deck (31):
1

What three characteristics are necessary for a classification of malignant?

1. Abnormal cells
2. Dividing without control
3. Can invade nearby tissues

2

What are the six hallmarks of cancer?

1. Evading apoptosis
2. Self-sufficiency in growth signals
3. Insensitivity to anti-growth signals
4. Tissue invasion and metastasis
5. Limitless Replicative potential
6. Sustained angiogenesis

3

Describe the result of cancers ability to evade apoptosis.

the inherent cell suicide program is important in normal developmental processes, and in adults, apoptosis can serve as a safety net of sorts, because normal cells that accumulate excessive DNA damage undergo apoptosis. Unlike normal cells, cancer cells are resistant to apoptosis, and thus they continue to grow and divide even as they accumulate mutations.

4

Describe what is meant by cancers self-sufficiency in growth signals.

cancer cells no longer need to receive positive growth signals from other cells and tissues. Instead, cancer cells can either make their own growth hormones or they have changed so that they behave as if a growth stimulus were present even in the absence of growth hormone.

5

Describe the importance of insensitivity to anti-growth signals for cancer.

inability to respond normally to cues that regulate growth. For example, many cells in a healthy adult body are not actively dividing, because they are receiving signals telling them not to grow. Many cancer cells become insensitive to such anti-growth signals, thus fueling their uncontrolled growth and division.

6

Explain the concept of tissue invasion and metastasis.

In order for cancer to spread, cells must acquire mutations that turn on genes which allow them to break free from the primary tumor, travel through the blood stream, and establish a new colony of cells at another site in the body (ability comes from 2 and 3).

7

Explain how cancer achieves a limitless replicative potential.

Cancer cells can lengthen their telomeres (by turning on telomerase), thus allowing them to divide an indefinite number of times

8

Why is it important for cancer to have sustained angiogenesis?

the growth and division of a community of cells that has acquired some of the hallmarks of cancer will stall unless that tiny tumor figures out how to get the nutrients it needs to fuel continued growth and division. This process of recruiting new blood vessels is called angiogenesis.

9

Explain the normal role of a tumor suppressor gene. What happens when this is mutated? How many mutations are normally necessary in cancer?

inhibit cell wall proliferation or stimulate apoptosis when needed. Gene protects a cell from progressing towards cancer. Mutations of tumor suppressor genes cause a loss or reduction in function. Normally need damage to both genes to cause cancer.

10

A mutation in what produces an oncogene? What does this result in?

mutation of a normal proto-oncogene which stimulates cell proliferation. Mutagens, Carcinogens, Viruses, Irradiation and Genetic Predisposition transform a normal proto-oncogene which are essential for cellular functions into the cellular oncogene which is responsible for altered cellular functions leading to a spontaneous neoplasm.

11

What type of protein becomes an oncogene?

Growth factors, growth factor receptors and signal transducing proteins.

12

Are tumor suppressor mutations dominant or recessive?

Recessive.

13

A germ-line mutation involves which cells? Why?

All of your cells because it is hereditary.

14

Somatic gene mutations involve which cells? Why?

Affected cells because the variations are often due to the environment. Not hereditary.

15

Are proto-oncogene mutations dominant or recessive?

Dominant.

16

What is the role of p53 in tumor suppression?

a. P53 is the most classic tumor suppressor gene. Its role is to prevent cells with damaged DNA from proliferating often referred to as the “guardian of the genome.” About have of people with cancer have p53 mutations. During the interphase portion of the cell cycle we have the G1 (growth) phase followed by the “p53 checkpoint” before the S (DNA synthesis) and subsequent G2 (growth) phase prior to the mitotic phase. So we have DNA damage, which activates p53 which decides whether the damage is reparable or irreparable. The response to reparable damage includes cell cycle arrest and DNA repair. The response for irreparable damage includes apoptosis.

17

What are the three types of conventional cancer therapies?

Surgery, Radiation and Chemo

18

What is the general target of methotrexate? Okay, what is the more specific target?

Stops the synthesis of the pre-DNA molecule building blocks. Normally, folate is taken up by the cell and must be reduced to FH2 and then to FH4 by DHFR for the production of thymidine and other nucleosides. Methotrexate has a higher affinity for DHFR than FH2 and therefore depletes intracellular FH4 which is necessary to methylate DUMP into DTMP which is a monomer required for DNA synthesis.

19

What class of medication is doxorubicin contained under?

Cytotoxix Antibiotics

20

What is the general target of doxorubicin? Okay, what is the more specific target?

Interfere with DNA replication and transcription. Doxorubicin inhibits topoisomerase II. Topoisomerase II cuts both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication.

21

What is the general target of cyclophosphamide? Okay, what is the more specific target?

Target: Directly damage the DNA in the nucleus of the cell preventing replication. Alkylating agents attach an alkyl group creating intrastrand linking and cross linking of the guanine DNA base preventing the DNA polymerase from being able to cut through them.

22

What kind or agent is cyclophosphamide?

Alkylating

23

What class of drugs does vincristine fall under?

Vinca alkaloids

24

What is the general target of vincristine? Okay, what is the more specific target?

Target: Effect the synthesis or breakdown of the mitotic spindles. Vinca alkaloids prevent tubulin from forming into microtubules which is necessary for cellular division. Spindles are used in mitosis and are made of microtubules without these microtubules sister chromatids cannot be pulled apart.

25

What was the one example of hormone therapy (targeted therapy)? What is its MOA?

Tamoxifen: Is a pro-drug, its active metabolite is an antagonist at the estrogen receptor. When Tamoxifen binds to an estrogen receptor the estrogen receptor does not acquire a changed shape which then inhibits it from binding to co-activators responsible for proliferation.

26

What were the two examples of monoclonal antibody (targeted) therapy?

CetuxiMAb
BevacuziMAb

27

What is the MOA of cetuxiMAb?

Blocks growth signals by blocking the EGFR receptor from being bound by a ligand that would cause pathways to be activated resulting in uncontrolled proliferation.

28

What is the MOA of BevacuziMAb?

Stops new blood vessels from forming. Blood vessels are needed to provide tumors with nutrients.

29

What are the two examples of tyrosine-kinase inhibitors?

Vemurafenib (PLX4032)
Gleevec (Imatinib)

30

What is the MOA of Vemurafenib?

Vemurafenib (PLX4032): Treats patients with BRAFV600E mutations. BRAF is mutated in 80% of melanomas with a common mutation being BRAFV600E (greater than 60%) which causes a constitutive activation in BRAF which activates MEK, which with ATP activates ERK which results in cellular proliferation.

31

What is the MOA of Gleevec?

Competitively binds to the ATP binding site of BCR-ABL inhibiting kinase ability. Gleevec competitively binds to site and inhibits protein. The substrate cannot enter the kinase site and the tumor cell cannot proliferate.