Oncology Flashcards
the cell cycle
G0 - cell is at rest
G1 - cell enters cell cycle, prepare for DNA replication, proto-oncogenes are activated
S - synthesis of structure and move to opposite poles; nuclear membranes develop around the separate sets of 23 pairs
G2 - cells prepare to divide
M - mitosis is completed and 2 daughter cells are created
cancer cells
No checkpoints - no DNA errors recognized, no apoptosis
disregard growth inhibitors of neighboring cells
they accumulate on top, around, and beside each other, crowding out, taking over normal cells and may break free and travel elsewhere
why does tumor development become easier as we age
strength of immune system decreases
well-differentiated
a cancer cell that looks and functions like a normal cell
anaplasia
indicates total cellular disorganization, abnormal cell appearance, & cell dysfunction
cancer cells break all these characteristics of normal cells
Contact inhibition Cohesiveness - "I'm out of here" Communication - little to none Proliferation control Proliferation rate "Self" HLA antigens
TNM system of staging cancer
T - tumor size, location, involvement
N - lymph node involvement
M - metastasis
T
Tumor size & location
T0 - no evidence of primary tumor
TIS - tumor in situ
T1-4 - progressive increase in size or involvement
N
Spread to nodes
N0 - no spread to regional lymph nodes
N1 - spread to closest or small number of regional lymph nodes
N2 - spread to most distant or numerous regional lymph nodes
M
metastasis
M0 - none
M1 - Yes
four stages of carcinogenesis
initiation - alteration of genes that arise spontaneously
promotion - actively proliferating cells accumulate → reversible
progression - cells undergo further mutation → tend to be more invasive w/ metastatic potential
metastasis
tumor suppression genes
these are the brakes
if these become inactivated, cells proliferate because there are no brakes
oncogenes
these are mutated proto-oncogenes
gas pedal
growth signal on permanently, gas pedal is stuck
p53 gene
tumor suppression gene in cells that controls cellular apoptosis (natural death of cells with damaged DNA)
promoters
help the mutated gene proliferate
examples:
- diet (high fat)
- ETOH
- tobacco
- hormones (long-term exposure to estrogen)
viral induced cancer
MOA- always involve the activation of growth-promoting pathways or inhibition of tumor suppressors in infected cells
cancer cells secrete ________________, a substance that gives them the capability to develop new blood vessels (angiogenesis)
vascular endothelial growth factor
cancer spread
seeding - tumor erodes & sheds into body cavities
implantation - direct expansion of tumor into adjoining tissue
metastasis - lymphatic & vascular
Common secondary site
liver bc the way the blood flows
lung cancer metastasizes to
bone - pain
brain - change in balance
colon cancer metastasizes to
liver - develop bleeding problems; ↑ liver enzymes
breast cancer metastasizes to
bone
brain
liver
lung - coughing, hemoptysis
prostate cancer metastasizes to
vertebrae - back pain
melanoma metastasizes to
brain
lung cancer
leading cause of cancer-related deaths (men & women) 70% present with advanced, or mets early diagnosis key to treatment most often > 65 yo blacks more often affected
lung cancer etiology
85% of lung cancer pts are current or former smokers
risk increases with higher “cigarette pack years”
patho of lung cancer
carcinogen overload genetic predisposition paralyze the cilia lesion development progresses to CA activation of oncogenes deactivation of tumor suppressor genes rapid proliferation, destruction, invasion
types of lung cancer
non-small cell lung cancer (NSCLC) - 85-90% of lung cancers, slow growing
small cell lung cancer (SCLC) - rapidly growing and mets quickly
S/S of lung cancer
cough hemoptysis wheeze or stridor chest pain dyspnea wt loss excessive fatigue weakness hoarseness obstructive accumulation of secretions in the brochioles that appear as PNA
paraneoplastic ACTH in lung cancer
tumor secretes ACTH, which resembles MSH, stimulating melanocytes, giving pt tanned appearance
breast cancer risk factors
> 50 prolonged reproductive life hormone replacement therapy obesity late childbirth (after 30) nulliparous (no pregnancies) family hx of breast or ovarian cancer ashkenazi jewish women BRCA1 & BRCA2 mutation
individuals with BRCA1 & BRCA2 mutations have an increased risk of what cancers?
breast ovarian colon pancreatic males ↑ risk of prostate
anti-cancer agents
cytotoxic agents
hormonal agents
biologicals
targeted drugs
cytotoxic agents = cell _________
death
hormonal agents →
block effects of hormones on tumor
biologicis →
alter the body’s response to cancer
targeted drugs →
newer class, targets cancer cells ONLY
growth fraction
the ratio of proliferating cells to resting cells
chemos work better on cells that are actively growing, dividing
malignant tumors initially grow ______________
very rapidly
as tumor increases in size, rate of proliferation __________
decreases ie. low growth fraction
Low growth fraction of tumors have what characteristics
- large tumors have a necrotic core
- ↓ nutrient supply at core
- more cells in resting phase (G0)
- more difficult to treat
consequences of late detection
mets
less responsive
patient more debilitated by disease
solid tumors respond poorly because
low growth fraction
limited blood supply
as tumor ages, heterogeneity ___________
increases
mutations become harder to treat
intermittent chemo goal
100% CA cell death with limited normal cell injury
try to strike a balance, letting normal cells recover but not too long
combo therapy
advantages:
-reduces drug resistance & normal cell injury (don’t want overlapping toxicities)
-increases cancer cell death
optimal dosing
- maximize results
- cell-cycle specific agents
- keep active drug present in body long enough to hit the cells when they enter the specific phase the drug is targeting
regional drug therapy
access to tumors
high drug concentrations
decrease systemic toxicity
examples: intraarterial, intrathecal, intravesical
usual chemo toxicities
N/V for several days after tx
1-2 weeks after first round:
↓ WBC, RBC, platelets
Diarrhea
alopecia
fatiguehyperuricemia toxicity with chemo
excessive level of uric acid in blood
cause: cell death/destruction of DNA
drugs to deal with chemo toxicities
odansetron (Zofran) - serotonin receptor antagonist
promethazine (phenergan) - H1 receptor antagonist
dexamethasone
magic mouthwash
cell cycle phase specific
work only at a specific phase in cell cycle
does not affect G0 phase
prolonged infusion bc must capture each cell entering the phase it’s targeting
cell-cycle phase non-specific
works on all stages (including G0)
not as effective in injury to the proliferating cell
cytotoxic agents
largest class of chemo drugs (targets high growth fraction cells)
moa: disrupt dna synthesis, disrupt mitosis
Examples: alkylating agents antimetabolites antitumor abx mitotic inhibitors misc.
alkylating agent
cyclophosphamide
cell cycle phase non-specific
resistance
usual toxicities plus: vesicant hemorrhagic cystitis sterility discoloration of skin & nails
antimetabolite
methotrexate
moa: folate antagonist
cell cycle specific (typlically S phase)
resemble natural metabolites
resistance
usual toxicities plus:
nephrotoxic
hepatotoxic
fetal death & abnormalities
antitumor abx
doxorubicin
cell cycle phase nonspecific
usual toxicities plus:
cardiotoxic (sometimes fatal); acute and delayed
harmless red color to urine/sweat
vinca alkaloids
vincristine
cell cycle specific (blocks mitosis)
usual toxicities plus:
peripheral neuropathy
vesicant
no bone marrow suppression in some drugs of this class
ondansetron
serotonin antagonist
treats N/V
blocks serotonin receptors on vagal nerve and in the CTZ
AE: HA, D, dizziness
efficacy improved with steroids
promethazine
dopamine antagonist
N/V
blocks dopamine receptors in CTZ
AE: respiratory depression, drowsiness, sedation, vesicant
black box: resp depression < 2 yo, gangrenous extravasation
biologics moa
uses body’s immune system to kill CA cells
stimulates body’s own immune system response by turning on or off the signals CA cells use to allude the immune system
biologic types
- immune checkpoint inhibitors - allow immune system to respond more strongly
- T-cell transfer therapy - boosts natural abilities of T-cells to fight CA
- monoclonal antibodies - mark CA cells
- treatment vaccines - boosts immune system’s response
- immune system modulators - enhance body’s immune response
biologics
SE
pain, swelling, soreness flu-like sxs weight gain/fluid retention diarrhea risk of infection
many SEs are d/t the revving up of immune response which can then also act on non-CA cells
CTZ
chemoreceptor trigger zone
