Case Study

Question 1

PD1/PD-L1

Answer 1

biomarkers to determine if certain pt is likely to benefit from immunotherapy
how useful are the clinical trial data from other types of cancers? (PD1 blockers were approved as a viable treatment for many types of cancers regardless of the biomarkers)
ex. ipilimumab: CTLA-4 inhibitor, strong mismatch dMMR
ex. PD-1 blockade with pembrolizumab may be effective in tumors with mismatch repair deficiency

Question 2

PD-1 blockers

Answer 2

pembrolizumab, nivolumab, cemiplimab

Question 3

PD-L1 blockers

Answer 3

atezolizumab, avelumab, durvalumab

Question 4

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

Answer 4

PD-L1

Question 5

BRAC1 and KRAS targeted therapies:

Answer 5

BRAC1: olaparib, niraparib, talazoparib, rucaparib
KRAS: binimetinib, trametinib, cobimetinib

Question 6

PARP inhibitor to treat cancer cells with BRCA1 mutations

Answer 6

both PARP and BRCA-mediated pathways can repair DNA
in BRCA-mutated cells, DNA repair can still occur via the PARP pathway, but the accuracy is low
by blocking PARP, both repair pathways are now disrupted, cannot repair DNA at all
synthetic lethality

Question 7

BRAC mutation is a ____ of function

Answer 7

loss
no homologous recombination, no repair –> cell death

Question 8

Synthetic lethality

Answer 8

a situation in which mutations (changes) in two genes together result in cell death, but a mutation in either gene alone does not.

Question 9

BRAC mutation in cancer

Answer 9

loss of function

Question 10

KRAS signaling pathway and target therapies

Answer 10

KRAS may activate the RAF-MEK pathway, thus could consider inhibitors for this pathway
KRAS may also activate the PI3K pathway, thus inhibitors for this pathway can also be considered

Question 11

AMG 510

Answer 11

first in class, small molecule that specifically and irreversibly inhibits KRAS G12C by locking it in an inactive GDP-bound state
can only bind to KRAS G12C

Question 12

CDKN2A/B loss

Answer 12

CDKN2A encodes 2 tumor supressors (p14ARF and p16INK4A); CDKN2B encodes tumor supressor (p15INK4B); these proteins are involved in CDK4/6 and MDM2 pathways; CDKN2A loss, releases inhibition of CDK4/6 pathway and MDM2 pathway, therefore cnacer cells might be sensitive to CDK4/6 inhibition

Question 13

CDK4 and CDK6 inhibitor

Answer 13

palbociclib, ribociclib, abemaciclib

Question 14

Ribociclib and Binimetinib for

Answer 14

melanoma patients with NRAS mutation