midterm key concepts Flashcards
what are PD-1 and PD-L1?
proteins (receptor and ligand pair) that play a role in the immune response and cancer immunotherapy
is PD-1 the receptor or the ligand?
receptor
is PD-L1 the receptor or the ligand?
ligand
do we measure PD-1 or PD-L1 to identify cancer in a patient
PD-L1
what is the goal of PD-1 blocker therapy?
antagonize this receptor and prevent PD-L1 from binding
what is the goal of PD-L1 blocker therapy?
prevent PD-L1 from binding to the receptor
what are PD-1 blocker drugs?
Pembrolizumab (Keytruda)
Nivolumab (Opdivo)
Cemiplimab (Libtayo)
what are PD-L1 blocker drugs?
Atezolizumab (Tecentriq)
Avelumab (Bavencio)
Durvalumab (Imfinzi)
if a BRCA-1 mutation exists, which drug therapy should we use?
PARP inhibitors
why do we use PARP inhibitors to treat cancer with BRCA-1 mutations?
BRCA-1 mutations decrease the completeness of cell repair. PARP inhibitors kill off the cell to prevent the cell from developing into cancer.
what is synthetic lethality?
drug-induced cell death
what are CDKN2A and CKDN2B?
tumor suppressors
which cyclin-dependent kinases are controlled by CDKN2A and CKDN2B?
CDK4 and CDK6
why can mutations in CDKN2A and CKDN2B be dangerous?
mutations in them cause an increased risk of cancer since it is no longer being suppressed
how can we treat a mutation in CDKN2A and CKDN2B to prevent the growth of cancer?
inhibit CDK4 and CDK6
what are CDK4 and CDK6 inhibitors?
palbociclib
ribociclib
abemaciclib
what are PARP inhibitor drugs?
olaparib
niraparib
talazoparib
rucaparib
how do KRAS mutations affect cell division/growth?
it causes uncontrolled cell division/growth
how can drug therapy treat consequences of KRAS mutations?
by introducing drugs that control cell division
what drugs can be used to control cell division in the presence of a KRAS mutation
binimetinib
trametinib
cobimetinib
what does AMG510 target?
KRASG12C
what is the most common KRAS mutation?
KRASG12V
what are the different types of drug therapies that target the immune system or cell divison?
RNA interference/ASOs
mRNA medicines
MABs and antibody-drug conjugates
gene therapy
CRISPR-mediated gene editing
what is RNA interference/ASOs?
drugs that decrease mRNA level, therefore protein production and expression
when do we use RNA interference/ASOs?
in cases of overexpression/hyperactivity
what are mRNA medicines?
medicines (usually vaccines) that use exogenous mRNA to program immune responses in patients
when do we use mRNA medicines
vaccines, specifically COVID
what are MABs and antibody-drug conjugates?
drugs that block receptors or deliver drugs directly
when do we use MABS and antibody-drug conjugates?
we use them in various disease states including cancer, transplants, infections, autoimmune disorders
what is gene therapy
direct treatment of a mutated gene
what do gene therapies use to deliver drug?
adeno-associated virus (AAV)
when do we use gene therapy?
to recover loss of function
what gene therapy is FDA approved
zolgensma- used to treat spinal muscular atrophy
what is CRISPR-mediated gene-editing?
direct editing of genetic mutations
is CRISPR-mediated gene-editing FDA approved?
not currently
what is stem cell therapy
theoretically could be used to replace or repair cells
how does PCSK9 affect serum LDL concentrations
PCSK9 binds to LDL-R and allows bound LDL to be absorbed from the blood stream and the whole receptor-ligand complex is degraded
how do PCSK9 mutations affect patients?
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)
what are PCSK9 inhibitor drugs?
repatha
praluent
what cells make antibodies?
B cells
what type of drug are repatha and praluent
monoclonal antibodies
what do we need to make a COVID vaccine?
sequence information of coronavirus spike protein
modified mRNA
lipid coating
what do we NOT need to make a COVID vaccine?
live COVID-19 particles
what are the important players in the polymerase chain reaction?
DNA template
dNTPS (A,T,C,G)
primers
buffer
enzyme: Taq polymerase
what is a statistically significant p value in normal studies?
< 0.05
what is a statistically significant p value in genomics studies?
</= 5x10^(-8)
what is linkage disequilibrium (LD)?
how often base pairs are inherited together
what do we use to measure LD?
R^2
what is LD if R^2=0?
no LD, infinite recombinations
what is LD if R^2=1?
complete/perfect LD, no recombinations
what is LD if R^2=0.8?
strong LD
what is the confidence interval (CI) set at for genomics studies?
95%
what risk is a patient at if CI>1?
significant risk
what risk is a patient at if CI contains/includes 1?
no statistical significance
what risk is a patient at if CI<1?
significant protective effect
which testing technology detects only known SNPs?
DNA chip
what is an advantage of DNA chip testing?
high throughput, low cost
which testing technologies detects both known and unknown SNPs?
sanger sequencing
next generation sequencing
what is a difference between sanger sequencing and next generation sequencing?
next generation sequencing is lower cost per base, but costs more total
what does it mean that next generation sequencings uses sequencing by synthesis in parallel?
synthesis at the same time
when should sanger sequencing be used?
when looking for 1 gene/area
when should next generation sequencing be used?
when looking at whole genome/exome
what is the difference between germline and somatic genes?
germline may be passed onto child, while somatic is not
how long do people have germline genes?
since birth
what could impact developing of somatic cells?
environment
what is a non-synonymous SNP?
a SNP that changes an amino acid
what is a synonymous SNP?
a SNP that does NOT change any amino acids
what is a missense SNP?
changes one AA, causes either loss or gain of function depending on AA
what is a nonsense SNP?
changes to a stop codon, normally causes loss of function
what is a silent SNP?
does not change AA, no change in function
what is a frameshift mutation?
an insertion or deletion that causes a downstream shift in codons (bad!)
