Pharmacogenomics

Question 1

How does Eteplirsen therapy work?

Answer 1

Used in DMD (Duchenne Muscular Dystrophy)

Exon skipping therapy (avoids SNP that places a pre-mature stop codon)

Skips Exon 51

Results in shorter, but 50% functional dystrophin protein

Question 2

How does Vitrakvi (Larotrectinib) therapy works?

Answer 2

Used in patients with solid tumours and test positive for NTRK gene fusions (can be used for a variety of cancers with this biomarker)

Question 3

How does Imatibib therapy work?

Answer 3

Used in leukemias caused by BCR-ABL gene fusion protein, BCR-ABL tyrosine kinase

It it inhibits proliferation and induces apoptosis in BCR-ABL positive cells

Question 4

What is the treatment strategy for stage I breast cancer?

Answer 4

1. Surgery (primary, remove small localized tumour)
2. Radiation therapy (to kill remaining cancer cells)
3. Hormonal therapy (If ER or PR positive)
4. Targeted therapy (HER2+ and high risk of recurrence)

Chemo not usually offerred

Question 5

What is the treatment strategy for stage II breast cancer?

Answer 5

1. Surgery (standard)
2. Chemo (adjuvant or neoadjuvant)
3. Hormonal
4. Targeted (HER2+)

Question 6

What is the difference between adjuvant and neoadjuvant chemo in stage II breast cancer therapy?

Answer 6

If tumour is big, then chemo is first and surgery is second(adjuvant)

If tumour is smaller, surgery is first then chemo (neoadjuvant)

Question 7

What are some examples of chemo therapies used in breast cancer?

Answer 7

• AC-T (Doxorubicin+cyclophophamide, followed by -taxel drugs)
• T-AC (-taxel drugs, followed by doxorubicin + cyclophosphamide)
• CAF (cyclophosphamide + doxorubicin + 5-FU)

Question 8

What is the treatment strategy for stage III breast cancer?

Answer 8

1. Chemotherapy (adjuvant and neoadjuvant)
2. Targeted therapy (HER2+, ER+, BRCA mutations)
3. Breast-conserving Surgery (before or after chemo)
4. Radiation therapy
5. Hormonal therapy (ER+ and PR+)

Question 9

What is the treatment strategy for stage IV breast cancer?

Answer 9

Goal is no longer to cure, instead to slow progression
1. Hormonal therapy (If ER+)
2. Chemo (monotherapy or combo therapy, depending on tolerability)
3. Targeted therapy (HER2+, BRCA)

Question 10

How are breast cancer types organized based on surface receptors?

Answer 10

Luminal A: ER+ and/or PR+, HER2-

Luminal B: ER+ and/or PR+, HER2+

HER2: ER-, PR-, HER2+

Triple negative: ER-, PR-, and HER2-

Normal-like: similar to Luminal A

Question 11

What is the mechanism of action for Tamoxifen?

Answer 11

Blocks estrogen from binding to estrogen receptors which has downstream effects of preventing the progression of the cell cycle (cytostatic)

Question 12

How does Palbociclib therapy work?

Answer 12

CDK4/6 inhibitor used in ER+ breast cancer

Block phosphorylation of Rb, which ultimately prevents cancer cells from passing the R point

Arrest cancer cells in G1 phase

Question 13

How does Trastuzumab therapy work?

Answer 13

Used in HER2+ breast cancer

Binds to subdomain IV of HER2 protein (sterically hinders binding of ligand to HER2)

Question 14

How does Pertuzumab therapy work?

Answer 14

Used in HER2+ breast cancer

Block dimerization of HER2

Inhibit HER2 signaling pathway and decrease cell growth

Question 15

How does T-DM1 therapy work?

Answer 15

Used in HER2+ breast cancer

Conjugate of trastuzumab (blocks HER2 ligand from binding) and emtansine (cytotoxic agent)

Question 16

How does Lapatinib therapy work?

Answer 16

Dual tyrosine kinase inhibitor for EGFR and HER2

Prevents phosphorylation and subsequent proliferating cascades)

Question 17

How does Gefitinib therapy works?

Answer 17

EGFR Inhibitor

Question 17

How does Cetuximab therapy work?

Answer 17

Monoclonal antibody against EGFR receptor (prevents activation by EGF)