lecture 1 mabe Flashcards
what are terminology of cancer?
Neoplasm: new growth (benign or malignant)
Tumor: nonspecific term for lump/swelling
Cancer: any malignant(can cause death) neoplasm
what are the types of plasias?
hyperplasia: increased size due to increased cells number
metaplasia: substitution of on adult tissue to another
dysplasia: abnormal proliferation leading to loss of architecture
anaplasia: dedifferentiation, cells dedifferentiate
what are the different types of cancer?
carcinoma
adenocarcinoma
sarcoma
lymphoma
melantoma
blastoma
teratoma
what is carcinoma/adenocarcinoma
carcinoma: neoplasm malignancies of sqamous epithelial cell origin
adenocarcinoma: malignant neoplasma of glandular origin
what is sarcoma?
malignant neoplasm of mesenchymal tissues
what is lymphoma/leukemia?
malignant neoplasm of hematopeoitic tissue
what is melanoma?
cancer in melanocytes –> skin/eyes
what is blastoma?
malignancies in precursor cells (blasts) –> often in children
what is teratoma?
germ cell neoplasm
what is TNM staging?
T: primary tumor
Tx: cannot evaluate
T0: no evidence
Tis: abnormal cells that may become cancer
T1,2,3,4: size/extent of invasion
N: regional lymph nodes
Nx: cannot evaluate
N0: no evidnce
N1,2,3: how many lymph node involved
M: distant metastasis
Mx: cannot evaluate
M0: no evidnce
M1: distant metastasis present
what is cancer grading?
GX: grade not assessed
G1: well differentiated (lowest grade)
G2: moderate differentiated (intermediate grade)
G3: poorly differentiated (high grade)
G4: undifferentiated (highest grade)
what are the three properties of cancer?
uncontrolled cell growth
tissue invasions
metastasis
what is v-Src?
an oncogene
RSV encodes for v-Src
what is a proto-oncogene?
any gene in a healthy cell that can promote tumor growth
what is retinoblastoma?
childhood retinal cancer
retinal cells dont stop diving during development
what is the 2-hit hypothesi?
hereditary retinoblastoma already has a single deletion
what is RB1?
a tumor supressor
can be expressed on either chromosome, but needs homo
heterozygous can be inherited
what is loss of heterozygosity?
predetermined bc they have 1 mutation already
what are the hallmarks of cancer?
can be either tumor suppressors or oncogenes
can prevent or promote cancer
what is the genetic basis of cancer?
time to cancer is decreased with increased mutation rate
what are BRCA genes?
BRCA1 + BRCA2 are tumor supressors
they encode for proteins that repair DNA
BRCA mutations in breast cancer increase susceptibility to PARP inhibitors
what is olaparib?
PARP inhibitor
for cancers with BRCA1/2 mutations
Binds to PARP to DNA and does not allow it to detach “trapping”
what is chemotherapy 5 year survival rate?
69%
only a few curable cancers: hodgkins, childhood leukemias, testicular cancers
what are the phases of the cell cycle?
G0/G1: getting building blocks for DNA replication
S: cell replicating DNA
G2: cell assembling machinery for segregation and cytokinesis
M: mitosis
what is the cell cycle driven by?
driven by cyclins paired with cyclin-dependent kinases
what is the R point?
restriction point is the critical time for cells to decide if they divide or not
right before S phase
what is palbociclib?
CKD4/6 inhibitor
targets G1 stage of cell cycle
approved for BRCA1/2 cancers
what are important proteins in cancer?
P53 - tumor supressor
RB1 - tumor supressor
P16 - tumor supressor
RAS - oncogene
Normal cell checkpoints?
Cells halt in G1 until DNA is repaired
cells then proceed into S
if cells proceed into S without repairing DNA, they apoptose
what drugs do not require cycling cells? effective at G0 phase and through cell cycle
DNA alkylating agents can damage DNA independent of cell cycling
what drugs are more effective in cycling cells?
alkylating agents and DNA intercalating agents
what is the best way to use chemo?
repeat administration + continous infusion
because cells are constantly cycling, higher doses wont be as effective
what are side effects of chemo?
chemo kills rapidly dividing cells
major dose limiting toxic: hematopeitic WBC - infections, platelet hemostatis, RBC anemia
GI: N/V, loss of appetite
what are chemotherapy limitations?
give dose intensive early
inverse relationship between tumor size and curability
combination therapies
(CHOP)
what is chemo combo therapy?
CHOP:
Cyclophosphamide (alkylating)
Doxorubicin (anthracycline)
Vincristine (microtubule)
Prednisone (steroid)
what are advantages for combo chemo?
no additive toxicity for drugs with non-overlapping toxicities
what are mechanisms of drug resistance?
increased efflux: PgP and MRP
reduced import
decreased activation of prodrug
increased detoxification of drug molecules
what are cell survival mechanisms?
activation of anti-apoptotic regulators
increased repair of damaged caused by chemo
what is the most common reason for resistance to multiple chemotherapies at once?
drug transport out of cells
what are limitations of chemo?
resistance and toxicity
