Lecture 16: Cancer Genetics and Gene Therapy

Question 1

gene therapy

Answer 1

• the delivery of therapeutic genes into patient’s cells

- goals is to correct genetic disease conditions caused by faulty genes

Question 2

translational medicine

Answer 2

translating scientific discoveries into effective therapy

Question 3

what is the criteria for gene therapy?

Answer 3

• the gene or genes involved in causing the disease have been identified
• the gene can cloned or synthesized in the lab

Question 4

what is the only gene therapy approved for diseases?

Answer 4

somatic cells

-enhancement, germline, and stem cell are not

Question 5

ex vivo gene therapy

Answer 5

• cells from a person with a genetic condition are removed
• treated in a lab
• translated back
• no immune response rejection

Question 6

in vivo gene therapy

Answer 6

• therapeutic DNA introduced into affected cells
• the challenge is restricting delivery to desired cells
• off target gene delivery is a problem

Question 7

viral vectors in gene therapy delivery strategies

Answer 7

DNA viruses, RNA viruses

Question 8

non-viral gene therapy delivery strategies

Answer 8

cationic polymers, dendrimers, cell penetrating peptides

Question 9

adenoviruses

Answer 9

• used in early gene therapy trials
• capable of carrying large number of genes
• there is a disadvantage because humans produce antibodies against adenoviruses, which would make the therapy ineffective

Question 10

how does adeno-associated viruses work as gene vecotrs?

Answer 10

• the vector is DNA

- RNA is translated into protein in the cytoplasm

Question 11

what are you making in gene therapy vectors?

Answer 11

-AAV particles (gene therapy vectors)

Question 12

what are the resulting vectors when making gene therapy vectors?

Answer 12

• are non-replicating because they do no have rep or cap genes
• they can infect target tissue and express their genes, but are defective to make more virus particles

Question 13

rAAV

Answer 13

recombinant AAV, these are replication incompetent

Question 14

where is cancer largely caused?

Answer 14

somatic cells

-only 5% of cancers are associated with germline mutations

Question 15

cancer: genetic disease

Answer 15

-genomic alterations with cancer include single-nucleotide substitutions, chromosomal arrangements, amplifications, and deletions

Question 16

cancer: genetic disease at somatic level

Answer 16

• results from mutated gene products ir abnormally expressed genes
• mutations affect multiple cellular functions

Question 17

what two fundamental properties do cancer cells have?

Answer 17

• abnormal cell growth and division

- metastatic spread

Question 18

benign tumors

Answer 18

• result from unregulated cell growth that forms a multicellular mass
• removed by surgery, causing no serious harm

Question 19

malignant tumors

Answer 19

-results from metastisized cells invading other tissue and causing life threatening problems

Question 20

clonal origin

Answer 20

all cancer cells in primary and secondary tumors are clonal

-by clonal, this is meaning originated from common ancestral cell that accumulated numerous specific mutations

Question 21

what does cancer require?

Answer 21

• multistep mutations
• age-related incidence of cancer indicated that cancer develops from accumulation of several mutagenic events in single cell
• incidence of most cancers rises exponentially with age
• independent and random mutations are necessary for cell to become malignant

Question 22

carcinogens

Answer 22

• cancer causing agents

- delay between exposure to carcinogen and appearance of cancer is an indication of the multistep process

Question 23

tumorigensis

Answer 23

• development of a malignant tumor
• result of two or more genetic alternations
• progressively release cells from normal controls on cell proliferation and malignancy

Question 24

interphase

Answer 24

• interval between mitotic division

- cell grows and replicates its DNA

Question 25

cells that stop proliferating eneter G0

Answer 25

- do not grow or divide but are metabolically active - cancer cells are unable to enter G0 and cycle continously - cells in G0 are stimulated to reenter cell cycle by external growth signals - signal transduction initiates gene expression that propels cell out of G0 and back into cell cycle

Question 26

G1/S, G2/M, and M checkpoints

Answer 26

- 3 distinct checkpoints where the cell monitors external signals and internal equilibrium - cells decide whether to proceed to the next stage of the cell cycle

Question 27

CDKs (cyclin-dependent kinases)

Answer 27

- regulation of cell-cycle progress is mediated by cyclins and cyclin-dependent kinases - regulate synthesis and destruction of cyclin proteins

Question 28

proto-oncogenes

Answer 28

genes whose products promote cell growth and division

Question 29

proto-oncogenes encode

Answer 29

- transcription factors that stimulate expression of other genes - signal transduction molecules that stimulates cell division - cell cycle regulators that move cell through cell cycle

Question 30

oncogenes

Answer 30

- is a proto-oncogene mutated or aberrantly expressed - has gain-of-function alteration - contributes to development of cancers - only one allele needs to be mutated or misexpressed to contribute to cancer

Question 31

tumor suppressor genes

Answer 31

regulate cell-cycle checkpoints and initiate process of apoptosis

Question 32

mutated tumor-suppressor genes

Answer 32

- are unable to respond to cell-cycle checkpoints or undergo apoptosis - this leads to more mutations and the development of cancer

Question 33

apoptosis

Answer 33

- programmed cell death - occurs when DNA or chromosomal damage is too severe to repair - cells halt process through cell cycle - prevents cancer - eliminates cells not contributing to final organism

Question 34

steps in apoptosis

Answer 34

- fragmentation of nuclear envelope - disruption of internal cellular structures - dissolution of cell into small, spherical apoptotic bodies - engulfing of apoptotic bodies by phagocytic cells