FINAL-- DNA Repair and Cancer therapies #14

Question 1

DNA Damage Responce (DDR)

Answer 1

Maintenance of genome integrity is essential for cell survival and the faithful transfer of genetic information. Eukaryotic cells evolved a DNA damage response (DDR) to sense, evaluate, and repair chromosome and DNA lesions or to direct cells for destruction when the harm is irreparable.

Question 2

Detection of DNA damage and activation of DNA repair

Answer 2

If a mutation is detected, the cell cycle will arrest and the mutation will be repaired before the cell re-enters the cell cycle, or the cell will enter apoptosis.
- p53 controls the process and Mdm2 negatively regulates p53

Question 3

p53 pathway

Answer 3

In a normal cell, p53 is inactivated by its negative regulator, mdm2. Upon DNA damage or other stresses, various pathways will lead to the dissociation of the p53 and mdm2 complex. Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell or apoptosis to discard the damaged cell. How p53 makes this choice is currently unknown

Question 4

DNA repair pathways

Answer 4

cellular responses that are associated with the restoration of the normal pair sequence and structure of damaged DNA
- 6 primary DNA repair pathways
- Series of biochemical events: sensing, excision, and restoration of the normal DNA sequence.

Question 5

Major Proteins involved with DNA repair include:

Answer 5

• Sensory (DNA binding) proteins
• Enzymes that remove damaged bases
• Enzymes that restore the normal DNA sequence
• Regulatory enzymes

Question 6

DNA repair pathways and cancer

Answer 6

• Cancer cells are often deficient in a normal DNA repair function and this
  deficiency allows the tumor to develop genomic instability.
  -

Question 7

With defective DNA repair, the tumor can:

Answer 7

􏰦 Break and reform chromosomes
􏰦 Generate new oncogenic fusion genes
􏰦 Disrupt tumor suppressor genes
􏰦 Amplify drug-resistance genes
􏰩 progress to a more malignant state.

Question 8

Cancer Therapies

Answer 8

• Surgery
• Radiation
• Hormonal therapy
• Chemotherapy
• Targeted therapy
• Immunotherapy

Question 9

Targeted therapy

Answer 9

Inhibits proteins that are mutated or overexpressed and helps the cancer to grow - this makes the therapy more cancer-specific

Question 10

Immunotherapy

Answer 10

Use of medicines to stimulate a patient’s immune system to recognize and destroy cancer cells more effectively

Question 11

Cytostatic drug

Answer 11

a drug that stops cell growth

Question 12

Cytotoxic drug

Answer 12

a drug that kills cells

Question 13

Chemosensitizer

Answer 13

inhibits normal DNA repair processes (limits toxicity)

Question 14

What happens if a tumor is defective in one pathway?

Answer 14

It may be hyper-dependent on a second pathway for its survival. Accordingly, a drug, such as a PARP inhibitor, that targets the second pathway may be selectively toxic to these tumors.