Final exam Flashcards
What are opioid conversions?
Morphine - 10mgIV = 30mgPO
Oxycodone - 20mgPO
Hydromorphone - 1.5mgIV = 7.5mgPO
What is length time bias?
Asymptomatic patients are more likely to have less aggressive malignancies, so screening appears to increase survival time
What factors affect the number needed to screen?
Frequency of testing
Prevalence of disease
Duration of follow-up
Cervical cancer screening guidelines
<21: no screening
21-65: pap q3y OR pap/HPV q5y (age 30+)
>65: no screening unless high risk
Breast cancer screening guidelines
40-49: pt discussion
50-74: q2y mammo
>75: no mammo
Lung ca screening guidelines
50-80 AND >20py OR currently smoking OR smoking in last 15 yrs = q1y LDCT
Prostate ca screening guidelines
55-69: joint decision making
>70: no screening
Colon ca screening guidelines
45-75: q10y colonoscopy
76-85: pt discussion
>85: no screening
What is the difference between Sanger and NGS?
Sanger: sequences one fragment at a time, good for small analysis
NGS: sequences millions of fragments simultaneously
What is a diagnostic biomarker? Example?
Characteristic that indicates what disease the patient has. Melan-a
What is a prognostic biomarker? Example
A marker that indicates risk of disease recurrence. Oncotype DX DCIS score
What is a predictive biomarker? Example
marker that indicates what treatment will most likely benefit the patient. NGS for solid tumors
what is a pharmacokinetic biomarker? example?
marker that indicates what drug dose should be given to the patient. G6PD for rasburicase.
How do you treat MSI-high CRC?
PD-1 blockade (pembro)
What molecular markers should you check for stage IV CRC?
KRAS, NRAS, BRAF, MSI, HER2 (BRHNK mnemonic)
How do you treat BRAF V600E stage IV CRC?
BRAF/MEK (can lead to phenotype switch to MMR deficient)
How do you treat HER2 stage IV CRC?
trastuzumab + TKI (better than TKI alone)
Why has KRAS been considered undruggable?
binding pocket on GTPase is hard to access, approaches have had high toxicity
How do you treat KRAS+ stage IV CRC?
Can use adagrasib + chemo (cetuximab)
MOA enzalutamide, darolutamide, apalutamide
binds to the androgen receptor to prevent androgen signaling
MOA abiraterone
blocks 17alpha-hydroxylase, reduces production of T
docetaxel MOA
inhibits microtubule formation (S phase)
MOA PARPis
stabilizes single-stranded DNA breaks, this inhibition gives time for a double-stranded break to form and the cell to apoptose
when do you test for somatic/germline mutations in prostate cancer?
metastatic disease
what is the ideal ratio of basal:demand for PCA?
2:1 (1:2 if prominent incident pain)
how do you determine basal rate for PCA?
determine total opioid in 24hr, convert to IV hourly rate, put 75% in basal considering cross-tolerance
what are three common mutations in AML?
DNMT3A (enzyme that catalyzes DNA methylation)
FLT3 (TK cytokine receptor)
IDH1
How does DNMT3A cause cells to be pre-leukemic?
biases fate decisions toward self-renewal rather than differentiation
what is 7+3 treatment?
common treatment for AML
7days cytarabine, 3 days daunorubicin
what is CPX-351?
a capsule containing both cytarabine and daunorubicin, delivers drug into the intracellular space, maintains ratio, does not rely on transporters
what is gemtuzimab? where does it bind?
a mab attached to chemotherapy (ozogamicin). binds CD33 –> brought into endosome, degraded by lysosome, chemo is released into the cytoplasm and can make its way to the nucleus
what is venetoclax?
blocks Bcl2, leading to cell death
used in AML
What is azacitidine
a hypomethylating agent (typically reserved for patients ineligible for induction
What is quizartinib? AEs?
FLT3 blocker for AML, QT prolongation
What is ivosidenib? AEs?
IDH1 blocker, differentiation syndrome
what is differentiation syndrome?
increased cytokine release and rapid differentiation of myeloid precursor cells. leads to fever, weight gain, peripheral edema, hypotension, acute renal failure, interstitial pulmonary infiltrates
what are the stages of multiple myeloma?
initiation –> MGUS –> smoldering myeloma –> MM (intramedullary to extramedullary)
what is bortezomib?
treatment for MM
binds proteosome, prevents degradation of pro-apoptotic factors, leads to programmed cell death
red flags for hereditary cancer
early age of diagnosis
same types of cancer in close relatives, multiple generations
less common cancers
multiple cancers associated with same gene
Ashkenazi Jewish
when is radiation therapy necessary post-mastectomy?
> =4LNs+ OR >=5cm
what patients are more likely to benefit from endocrine therapy than chemo?
lobular histology, low grade, strong ER expression, low oncotype score
list 4 actionable mutations in breast cancer
BRCA1/2 - PARPi
ESR1 - elecestrant
PIK3CA - alpelisib
PI3K, PTEN, AKT1 - capivasertib
what is pancreatic cancer association with depression?
tumors make IDO1, shunts tryptophan away from serotonin synthesis, instead makes kynurenine
What do you have to keep in mind with fluoxetine, paroxetine, bupropion use?
CYP2D6 inhibitors, interfere with tamoxifen
what are the four steps of pre-clinical drug discovery?
target identification
hit generation
lead generation
preclinical studies in animals
What are four characteristics important to be a successful drug candidate?
high potency
favorable pharmocokinetics
developability
good toxicity profile
How does a PROTAC work?
binding of E3 ligase to target protein, ubiquitination and destruction of protein
which cancers have the most diverse somatic mutations?
lung adenocarcinoma, stomach, head and neck
What mechanisms contribute to the mutational spectra of melanoma, GI tumors, lung cancer?
melanoma- w/ and w/o UV factors
GI tumors- w/ and w/o MMR
lung cancer- w/ and w/o exposure to environmental carcinogens (cigarette smoke)
Why do BRAF inhibitors not work in CRC?
EGFR is upregulated at baseline, mediates MAPK signaling through RAS shortly after deactivation of BRAF
What are the phases of CML?
Chronic (<10% blasts) - luekocytosis, hypercellular marrow
Advanced
Accelerated (10-19% blasts, basophils, platelets, splemomegaly)
Blast phase (<20% blasts)
what is the most frequent gatekeeper mutation in CML?
T315I
list mechanisms of acquired resistance to targeted therapy
gatekeeper mutations
bypass pathways
mutations in pathways downstream of oncogene
morphological change
persistence of cancer stem cells
changes in microenvironment
three genes most commonly mutated in SCLC?
RB1, p53, KMT2d (small park)
lung adenocarcinoma most common mutations
p53, EGFR, KRAS (peak-ras)
lung SCC most common mutations
p53, CDKN2A, KMT2d (pecks)
indications for immunotherapy in NSCLC
advanced: PDL1>50% pembro, PDL1<50% pembro+chemo, stage III, N2 and N3
side effects of checkpoint inhibitors
pneumonitis, myocarditis, myositis, nephritis, colitis, hepatitis
what is the warburg effect?
cancer cells replace normal oxygen respiration with fermentation of sugar
shunt pyruvate to lactate, foregoing the efficient oxidative phosphorylation for the quicker aerobic glycolysis
how does obesity lead to higher risk for cancer?
obesity causes chronic inflammation (oncogenic)
tumors activate oncogenes that lead to inflammation, obese tissue is conducive
high leptin:adiponectin ratio in adipose tissue creates an environment conducive to cell proliferation
how does estrogen drive ER+ breast cancer
ER dependent: binds to ER, acts as TF for genes including MYC, Bcl2, and FOXM1
ER independent: metabolism of estrogen in cytoplasm leads to metabolites with genotoxic effects
what are effects of phytoestrogens on the estrogen receptor?
low concentrations in vitro: promote tumor growth
high concentrations in vitro: inhibit tumor growth
what are the steps involved in metastasis?
development of metastatic cell
establishment of premetastatic niche
motility and invasion
intravasation
dissemination and transport
cellular arrest, vascular adhesion, extravasation
colonization
name 3 ways surgery can induce inflammatory responses
immunosuppression (systemic)
NETs - associated with metastatic risk
neovascularization
nonsynonymous mutation that leads to cancer?
PTEN
common copy number variant?
HER2
common in/del?
EGFR exon 19 del
common frameshift mutation
PTEN c800delA (premature stop codon)
common splice site mutation
KIT in GIST
common structural variant
ALK fusion in NSCLC
how is sanger sequencing used in cancer (specific example)?
1790T>G in BRAF
primary goals of cancer phase I trials
identify DLT and MTD
