BIO2: How do Cancers Grow?

Question 1

Cells can double _____ times in culture

What is the Hayflick limit?

Answer 1

20-60

Cell replicate up to that before cell division stops

Question 2

Define senescence

Answer 2

Cellular old age

Question 3

What are Telomeres?

Answer 3

Repetitive regions (nucleotide sequences) @ each end of a chromosome

Question 4

Each time a cell divides, its telomere gets _____.

Answer 4

Shorter

Unless telomerase (enzyme) is active + restores them

Question 5

Where are telomerase present?

Answer 5

Germ cells + rapidly dividing somatic cells

Pluripotent stem cells has regulated telomerase activity - Loss of activity over time leads to shorter telomeres

Question 6

Reverse transcriptase contains an RNA template.

What does the RNA template do?

Answer 6

Adds ‘TTAGGG’ repeats to chromosome ends

Question 7

Telomerase is detectable.

What % of malignant cells express telomerase?

Answer 7

90%

Question 8

When DNA is replicated, RNA primers tell DNA polymerase where to start. RNA primers is then degraded.

Why?

Answer 8

DNA polymerase fills internal gaps left by primer

Terminal gaps left leads to single stranded chromosome ends

Question 9

Germline cells + embryonic cells retain telomere length.

Why?

Answer 9

Due to expression of telomerase

Question 10

What cells lack telomerase?

Answer 10

Normal ccells

Telomeres shorten @ each division until they stop working

Question 11

What happens when normal cell cycle gets disrupted?

Answer 11

Cells continue to divide until they reach crisis

Question 12

How do cells escape crisis?

Answer 12

Activating telomerase (or alternative telomere lengthening)

Question 13

Describe alternative telomere lengthening

Answer 13

• Cells don’t express telomerase
• Recombination/fusion between ends of different chromosomes
• Cells that survive telomere shortening have chromosome rearrangements
• Oncogenic changes

Question 14

What are the different types of receptors?

Give an example for each.

Answer 14

• Enzyme coupled receptors - receptor tyrosine kinase
• Steroid-hormone receptors - estrogen receptor
• G-protein coupled receptors - not a target for anti-cancer drugs

Question 15

What is signalling?

Answer 15

How cells communicate with each other?

Question 16

What drugs target EGFR?

Answer 16

Cetuximab - stop EGF binding to EGFR (an antibody that blocks the receptor)

Erlotinib + Gefitinib - blocks activation

Question 17

Some EGFR mutations that promote cancer make EGR more sensitive to erlotinib + gefitinib.

How do we determine what drug patient can use?

Answer 17

Viewing patients cancer DNA sequence

Question 18

Mutations can cause drug sensitivity + resistance

Give examples of these mutations

Answer 18

EGFR mutations

Downstream signalling mutations

Both cause resistance to drug treatment

Question 19

How can we make it difficult for cancer cells to become resistant to therapy?

Answer 19

Hit cancers with combination of treatments

• Large numbers of cells in cancer makes it likely for resistant to be acquired agonist against single therapy
  
  • Single resistant clone can proliferate quickly
• For resistance to occur against 2 or more therapies, multiple mutations must occur in same cell

Question 20

Where do steroid hormones come from?

Answer 20

Cholesterol

• Diffuse into cells
• Transcription factors are activated by steroid hormone

Question 21

Estrogen receptor is a type 1 steroid hormone receptor.

Where is it activated?

Answer 21

In cytoplasm

• Ligand diffuses into cell
• Binds to receptor, displaces associated chaperone rpoteins
• ER dimerises + migrates to nucleus
• ER dimer links with co-activators or co-repressors to modify transcription of target genes