midterm key concepts

Question 1

what are PD-1 and PD-L1?

Answer 1

proteins (receptor and ligand pair) that play a role in the immune response and cancer immunotherapy

Question 2

is PD-1 the receptor or the ligand?

Answer 2

receptor

Question 3

is PD-L1 the receptor or the ligand?

Answer 3

ligand

Question 4

do we measure PD-1 or PD-L1 to identify cancer in a patient

Answer 4

PD-L1

Question 5

what is the goal of PD-1 blocker therapy?

Answer 5

antagonize this receptor and prevent PD-L1 from binding

Question 6

what is the goal of PD-L1 blocker therapy?

Answer 6

prevent PD-L1 from binding to the receptor

Question 7

what are PD-1 blocker drugs?

Answer 7

Pembrolizumab (Keytruda)
Nivolumab (Opdivo)
Cemiplimab (Libtayo)

Question 8

what are PD-L1 blocker drugs?

Answer 8

Atezolizumab (Tecentriq)
Avelumab (Bavencio)
Durvalumab (Imfinzi)

Question 9

if a BRCA-1 mutation exists, which drug therapy should we use?

Answer 9

PARP inhibitors

Question 10

why do we use PARP inhibitors to treat cancer with BRCA-1 mutations?

Answer 10

BRCA-1 mutations decrease the completeness of cell repair. PARP inhibitors kill off the cell to prevent the cell from developing into cancer.

Question 11

what is synthetic lethality?

Answer 11

drug-induced cell death

Question 12

what are CDKN2A and CKDN2B?

Answer 12

tumor suppressors

Question 13

which cyclin-dependent kinases are controlled by CDKN2A and CKDN2B?

Answer 13

CDK4 and CDK6

Question 14

why can mutations in CDKN2A and CKDN2B be dangerous?

Answer 14

mutations in them cause an increased risk of cancer since it is no longer being suppressed

Question 15

how can we treat a mutation in CDKN2A and CKDN2B to prevent the growth of cancer?

Answer 15

inhibit CDK4 and CDK6

Question 16

what are CDK4 and CDK6 inhibitors?

Answer 16

palbociclib
ribociclib
abemaciclib

Question 17

what are PARP inhibitor drugs?

Answer 17

olaparib
niraparib
talazoparib
rucaparib

Question 18

how do KRAS mutations affect cell division/growth?

Answer 18

it causes uncontrolled cell division/growth

Question 19

how can drug therapy treat consequences of KRAS mutations?

Answer 19

by introducing drugs that control cell division

Question 20

what drugs can be used to control cell division in the presence of a KRAS mutation

Answer 20

binimetinib
trametinib
cobimetinib

Question 21

what does AMG510 target?

Answer 21

KRASG12C

Question 22

what is the most common KRAS mutation?

Answer 22

KRASG12V

Question 23

what are the different types of drug therapies that target the immune system or cell divison?

Answer 23

RNA interference/ASOs
mRNA medicines
MABs and antibody-drug conjugates
gene therapy
CRISPR-mediated gene editing

Question 24

what is RNA interference/ASOs?

Answer 24

drugs that decrease mRNA level, therefore protein production and expression

Question 25

when do we use RNA interference/ASOs?

Answer 25

in cases of overexpression/hyperactivity

Question 26

what are mRNA medicines?

Answer 26

medicines (usually vaccines) that use exogenous mRNA to program immune responses in patients

Question 27

when do we use mRNA medicines

Answer 27

vaccines, specifically COVID

Question 28

what are MABs and antibody-drug conjugates?

Answer 28

drugs that block receptors or deliver drugs directly

Question 29

when do we use MABS and antibody-drug conjugates?

Answer 29

we use them in various disease states including cancer, transplants, infections, autoimmune disorders

Question 30

what is gene therapy

Answer 30

direct treatment of a mutated gene

Question 31

what do gene therapies use to deliver drug?

Answer 31

adeno-associated virus (AAV)

Question 32

when do we use gene therapy?

Answer 32

to recover loss of function

Question 33

what gene therapy is FDA approved

Answer 33

zolgensma- used to treat spinal muscular atrophy

Question 34

what is CRISPR-mediated gene-editing?

Answer 34

direct editing of genetic mutations

Question 35

is CRISPR-mediated gene-editing FDA approved?

Answer 35

not currently

Question 36

what is stem cell therapy

Answer 36

theoretically could be used to replace or repair cells

Question 37

how does PCSK9 affect serum LDL concentrations

Answer 37

PCSK9 binds to LDL-R and allows bound LDL to be absorbed from the blood stream and the whole receptor-ligand complex is degraded

Question 38

how do PCSK9 mutations affect patients?

Answer 38

mutations in PCSK9 allow the LDL-R to be recycled, meaning that more LDL can be removed from the blood stream (overall, benefits the patient)

Question 39

what are PCSK9 inhibitor drugs?

Answer 39

repatha praluent

Question 40

what cells make antibodies?

Answer 40

B cells

Question 41

what type of drug are repatha and praluent

Answer 41

monoclonal antibodies

Question 42

what do we need to make a COVID vaccine?

Answer 42

sequence information of coronavirus spike protein modified mRNA lipid coating

Question 43

what do we NOT need to make a COVID vaccine?

Answer 43

live COVID-19 particles

Question 44

what are the important players in the polymerase chain reaction?

Answer 44

DNA template dNTPS (A,T,C,G) primers buffer enzyme: Taq polymerase

Question 45

what is a statistically significant p value in normal studies?

Answer 45

< 0.05

Question 46

what is a statistically significant p value in genomics studies?

Question 47

what is linkage disequilibrium (LD)?

Answer 47

how often base pairs are inherited together

Question 48

what do we use to measure LD?

Answer 48

R^2

Question 49

what is LD if R^2=0?

Answer 49

no LD, infinite recombinations

Question 50

what is LD if R^2=1?

Answer 50

complete/perfect LD, no recombinations

Question 51

what is LD if R^2=0.8?

Answer 51

strong LD

Question 52

what is the confidence interval (CI) set at for genomics studies?

Answer 52

95%

Question 53

what risk is a patient at if CI>1?

Answer 53

significant risk

Question 54

what risk is a patient at if CI contains/includes 1?

Answer 54

no statistical significance

Question 55

what risk is a patient at if CI<1?

Answer 55

significant protective effect

Question 56

which testing technology detects only known SNPs?

Answer 56

DNA chip

Question 57

what is an advantage of DNA chip testing?

Answer 57

high throughput, low cost

Question 58

which testing technologies detects both known and unknown SNPs?

Answer 58

sanger sequencing next generation sequencing

Question 59

what is a difference between sanger sequencing and next generation sequencing?

Answer 59

next generation sequencing is lower cost per base, but costs more total

Question 60

what does it mean that next generation sequencings uses sequencing by synthesis in parallel?

Answer 60

synthesis at the same time

Question 61

when should sanger sequencing be used?

Answer 61

when looking for 1 gene/area

Question 62

when should next generation sequencing be used?

Answer 62

when looking at whole genome/exome

Question 63

what is the difference between germline and somatic genes?

Answer 63

germline may be passed onto child, while somatic is not

Question 64

how long do people have germline genes?

Answer 64

since birth

Question 65

what could impact developing of somatic cells?

Answer 65

environment

Question 66

what is a non-synonymous SNP?

Answer 66

a SNP that changes an amino acid

Question 67

what is a synonymous SNP?

Answer 67

a SNP that does NOT change any amino acids

Question 68

what is a missense SNP?

Answer 68

changes one AA, causes either loss or gain of function depending on AA

Question 69

what is a nonsense SNP?

Answer 69

changes to a stop codon, normally causes loss of function

Question 70

what is a silent SNP?

Answer 70

does not change AA, no change in function

Question 71

what is a frameshift mutation?

Answer 71

an insertion or deletion that causes a downstream shift in codons (bad!)