Pharmacogenomics HW 1 Notecards Flashcards

1
Q

What condition was covered in the homework?

A

Pancreatic adenocarcinoma

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2
Q

What are PD1 and PD-L1?

A

Biomarkers to determine if a certain patient is likely to benefit from immunotherapy

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3
Q

When would you use PD1/PD-L1 blockers as treatment?

A

-If either of these biomarkers have increased expression in cancer

-If there is a very strong mismatched repair deficit (MMR)

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4
Q

Why do T cells not kill cancer cells?

A

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

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5
Q

Where is PD-1 expressed?

A

T cells

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6
Q

Where is PD-L1 expressed?

A

Cancer cells

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7
Q

Should a doctor order a test to check the PD1 or PD-L1 expression in a tumor sample?

A

PD-L1

(PD1 is not present in the tumor sample, found on T cells)

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8
Q

What do PD1 levels tell us?

A

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

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9
Q

How do we decide whether to use a PD1 blocker or a PD-L1 blocker?

A

Look at clinical trials

-results can vary based on types of cancer, some respond better to certain blockers

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10
Q

What does Avelumab (Bavencio) block?

A

PD-L1

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11
Q

What does Durvalumab (Imfinzi) block?

A

PD-L1

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12
Q

What does Pembrolizumab (Keytruda) block?

A

PD-1

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13
Q

What does Atezolizumab (Tecentriq) block?

A

PD-L1

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14
Q

What does Nivolumab (Opdivo) block?

A

PD-1

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15
Q

What does Cemiplimab (Libtayo) block?

A

PD-1

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16
Q

What are the PD-1 blockers?

A

Pembrolizumab (Keytruda)

Nivolumab (Opdivo)

Cemiplimab (Libtayo)

17
Q

What are the PD-L1 blockers?

A

Atezolizumab (Tecentriq)

Avelumab (Bavencio)

Durvalumab (Imfinzi)

18
Q

What drugs are used to treat cancer cells with BRCA1 mutations?

A

PARP inhibitors

19
Q

What are the PARP and BRCA-mediated pathways used for?

A

To repair DNA

20
Q

True or False: In BRCA-mutated cells, the PARP pathway still can occur

A

TRUE, but accuracy is low

21
Q

What is a problem with having both the BRCA and PARP pathways blocked?

A

Both DNA repair pathways are disrupted (neither one running)

**cell dies

22
Q

What is synthetic lethality?

A

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)

23
Q

What kind of DNA break is repaired by PARP?

A

Single-strand breaks

24
Q

What kind of DNA break is repaired by BRCA?

A

Double-strand breaks

*done through homologous recombination

25
Q

Why are PARP and BRCA inhibitors effective?

A

Only cancer cells have the mutated PARP or BRCA so blocking these can lead to cancer cell death without affecting other cells

26
Q

In cancer cells, are BRAC/PARP gain-of-function or loss-of-function mutations more common?

A

Loss-of-function

*DNA not repaired, more mutations

27
Q

True or False: KRAS therapy directly targets KRAS

A

False

-target downstream proteins

28
Q

What drugs target BRAC1?

A

Olaparib
Niraparib
Talazoparib
Rucaparib

29
Q

What drugs target KRAS?

A

Binimetinib
Trametinib
Cobimetinib

30
Q

What pathways are activated by KRAS?

A

RAF-MEK pathway

PI3K pathway

**consider inhibitors for these

30
Q

What KRAS mutation is targeted by AMG 510?

A

KRAS-G12C

*note: in the homework they had G12V

31
Q

What is CDKN2A?

A

Important cell surface protein that inhibits CDK4 and CDK6 which are important for cell proliferation!

*without CDKN2A, there is nothing to inhibit cell proliferation

32
Q

What is the function of CDK4 and CDK6?

A

Cell proliferation

33
Q

When CDKN2A has a loss of function mutation, what do we do?

A

Need to artificially inhibit CDK4 and CDK6

34
Q

What are the CDK4 and CDK6 inhibitors?

A

Palbociclib
Ribociclib
Abemaciclib

35
Q

What combination therapy can be used in melanoma patients with NRAS mutations?

A

Ribociclib (Kisqali) + Binimetinib (Mektovi)