Pharmacogenomics HW 1 Notecards Flashcards
What condition was covered in the homework?
Pancreatic adenocarcinoma
What are PD1 and PD-L1?
Biomarkers to determine if a certain patient is likely to benefit from immunotherapy
When would you use PD1/PD-L1 blockers as treatment?
-If either of these biomarkers have increased expression in cancer
-If there is a very strong mismatched repair deficit (MMR)
Why do T cells not kill cancer cells?
Cancer cells express PD-L1 which interacts with PD-1 on T cells
*this sends signals to the T cell which makes it think that the cancer cell is a normal healthy cell
**this is why we want to either block PD-1 on the T cell or PD-L1 on the cancer cell, so this interaction does not occur
Where is PD-1 expressed?
T cells
Where is PD-L1 expressed?
Cancer cells
Should a doctor order a test to check the PD1 or PD-L1 expression in a tumor sample?
PD-L1
(PD1 is not present in the tumor sample, found on T cells)
What do PD1 levels tell us?
How many T cells have migrated to the cancer cells
**Does not affect clinical decision making because we do not know anything about what the cancer cells are expressing
How do we decide whether to use a PD1 blocker or a PD-L1 blocker?
Look at clinical trials
-results can vary based on types of cancer, some respond better to certain blockers
What does Avelumab (Bavencio) block?
PD-L1
What does Durvalumab (Imfinzi) block?
PD-L1
What does Pembrolizumab (Keytruda) block?
PD-1
What does Atezolizumab (Tecentriq) block?
PD-L1
What does Nivolumab (Opdivo) block?
PD-1
What does Cemiplimab (Libtayo) block?
PD-1
What are the PD-1 blockers?
Pembrolizumab (Keytruda)
Nivolumab (Opdivo)
Cemiplimab (Libtayo)
What are the PD-L1 blockers?
Atezolizumab (Tecentriq)
Avelumab (Bavencio)
Durvalumab (Imfinzi)
What drugs are used to treat cancer cells with BRCA1 mutations?
PARP inhibitors
What are the PARP and BRCA-mediated pathways used for?
To repair DNA
True or False: In BRCA-mutated cells, the PARP pathway still can occur
TRUE, but accuracy is low
What is a problem with having both the BRCA and PARP pathways blocked?
Both DNA repair pathways are disrupted (neither one running)
**cell dies
What is synthetic lethality?
UV light, sunlight, smoking, and other stress can cause a breakage of DNA
99% of time this can be fixed by repair mechanisms in the cell
**but this is a problem when DNA repair pathways are mutated (BRCA and PARP)
What kind of DNA break is repaired by PARP?
Single-strand breaks
What kind of DNA break is repaired by BRCA?
Double-strand breaks
*done through homologous recombination
