lecture 1 mabe

Question 1

what are terminology of cancer?

Answer 1

Neoplasm: new growth (benign or malignant)

Tumor: nonspecific term for lump/swelling

Cancer: any malignant(can cause death) neoplasm

Question 2

what are the types of plasias?

Answer 2

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

Question 3

what are the different types of cancer?

Answer 3

carcinoma
adenocarcinoma
sarcoma
lymphoma
melantoma
blastoma
teratoma

Question 4

what is carcinoma/adenocarcinoma

Answer 4

carcinoma: neoplasm malignancies of sqamous epithelial cell origin
adenocarcinoma: malignant neoplasma of glandular origin

Question 5

what is sarcoma?

Answer 5

malignant neoplasm of mesenchymal tissues

Question 6

what is lymphoma/leukemia?

Answer 6

malignant neoplasm of hematopeoitic tissue

Question 7

what is melanoma?

Answer 7

cancer in melanocytes –> skin/eyes

Question 8

what is blastoma?

Answer 8

malignancies in precursor cells (blasts) –> often in children

Question 9

what is teratoma?

Answer 9

germ cell neoplasm

Question 10

what is TNM staging?

Answer 10

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

Question 11

what is cancer grading?

Answer 11

GX: grade not assessed
G1: well differentiated (lowest grade)
G2: moderate differentiated (intermediate grade)
G3: poorly differentiated (high grade)
G4: undifferentiated (highest grade)

Question 12

what are the three properties of cancer?

Answer 12

uncontrolled cell growth
tissue invasions
metastasis

Question 13

what is v-Src?

Answer 13

an oncogene
RSV encodes for v-Src

Question 14

what is a proto-oncogene?

Answer 14

any gene in a healthy cell that can promote tumor growth

Question 15

what is retinoblastoma?

Answer 15

childhood retinal cancer
retinal cells dont stop diving during development

Question 16

what is the 2-hit hypothesi?

Answer 16

hereditary retinoblastoma already has a single deletion

Question 17

what is RB1?

Answer 17

a tumor supressor
can be expressed on either chromosome, but needs homo
heterozygous can be inherited

Question 18

what is loss of heterozygosity?

Answer 18

predetermined bc they have 1 mutation already

Question 19

what are the hallmarks of cancer?

Answer 19

can be either tumor suppressors or oncogenes
can prevent or promote cancer

Question 20

what is the genetic basis of cancer?

Answer 20

time to cancer is decreased with increased mutation rate

Question 21

what are BRCA genes?

Answer 21

BRCA1 + BRCA2 are tumor supressors
they encode for proteins that repair DNA
BRCA mutations in breast cancer increase susceptibility to PARP inhibitors

Question 22

what is olaparib?

Answer 22

PARP inhibitor
for cancers with BRCA1/2 mutations
Binds to PARP to DNA and does not allow it to detach “trapping”

Question 23

what is chemotherapy 5 year survival rate?

Answer 23

69%
only a few curable cancers: hodgkins, childhood leukemias, testicular cancers

Question 24

what are the phases of the cell cycle?

Answer 24

G0/G1: getting building blocks for DNA replication
S: cell replicating DNA
G2: cell assembling machinery for segregation and cytokinesis
M: mitosis

Question 25

what is the cell cycle driven by?

Answer 25

driven by cyclins paired with cyclin-dependent kinases

Question 26

what is the R point?

Answer 26

restriction point is the critical time for cells to decide if they divide or not
right before S phase

Question 27

what is palbociclib?

Answer 27

CKD4/6 inhibitor
targets G1 stage of cell cycle
approved for BRCA1/2 cancers

Question 27

what are important proteins in cancer?

Answer 27

P53 - tumor supressor
RB1 - tumor supressor
P16 - tumor supressor
RAS - oncogene

Question 28

Normal cell checkpoints?

Answer 28

Cells halt in G1 until DNA is repaired
cells then proceed into S
if cells proceed into S without repairing DNA, they apoptose

Question 29

what drugs do not require cycling cells? effective at G0 phase and through cell cycle

Answer 29

DNA alkylating agents can damage DNA independent of cell cycling

Question 30

what drugs are more effective in cycling cells?

Answer 30

alkylating agents and DNA intercalating agents

Question 31

what is the best way to use chemo?

Answer 31

repeat administration + continous infusion
because cells are constantly cycling, higher doses wont be as effective

Question 32

what are side effects of chemo?

Answer 32

chemo kills rapidly dividing cells
major dose limiting toxic: hematopeitic WBC - infections, platelet hemostatis, RBC anemia
GI: N/V, loss of appetite

Question 33

what are chemotherapy limitations?

Answer 33

give dose intensive early
inverse relationship between tumor size and curability
combination therapies
(CHOP)

Question 34

what is chemo combo therapy?

Answer 34

CHOP:
Cyclophosphamide (alkylating)
Doxorubicin (anthracycline)
Vincristine (microtubule)
Prednisone (steroid)

Question 35

what are advantages for combo chemo?

Answer 35

no additive toxicity for drugs with non-overlapping toxicities

Question 36

what are mechanisms of drug resistance?

Answer 36

increased efflux: PgP and MRP
reduced import
decreased activation of prodrug
increased detoxification of drug molecules

Question 37

what are cell survival mechanisms?

Answer 37

activation of anti-apoptotic regulators
increased repair of damaged caused by chemo

Question 38

what is the most common reason for resistance to multiple chemotherapies at once?

Answer 38

drug transport out of cells

Question 39

what are limitations of chemo?

Answer 39

resistance and toxicity