Lecture 10: Cancer 1

Question 1

cancer is a group of diseases in which cells develop malignant properties and become

Answer 1

1. aggressive
2. invasive
3. metastatic

Question 2

tumor

Answer 2

mad of abnormal growth of tissue, can be benign or malignant

Question 3

neoplasia

Answer 3

formation of presence of new, abnormal growth

Question 4

neoformation

Answer 4

new growth in reference to a tumor

Question 5

malignancy

Answer 5

cells that are

1. aggressive
2. invasive
3. metastatic

Question 6

bening tumors

Answer 6

self-limitind in their growth and do not invade or metastasize
(not aggressive, invasive, or metastatic)

Question 7

carcinoma

Answer 7

tissue of origin: epithelial tissue

Question 8

sarcoma

Answer 8

tissue of origin: bone, cartilage, muscle, fat, connective tissue

Question 9

leukemia

Answer 9

tissue of origin: bone marrow

Question 10

lymphoma

Answer 10

tissue of origin: immune system

Question 11

cns cancer

Answer 11

tissue of origin: brain and spinal cord

Question 12

melanoma

Answer 12

tissue of origin: melanocytes

Question 13

probability of being diagnosed with cancer

Answer 13

40%

Question 14

probability of dying of cancer

Answer 14

20%

Question 15

most common cancer types

Answer 15

• prostate
• lung
• breast
• colon, rectum

-pancreas (not that many cases but out of those cases majority die)

Question 16

probability of being diagnosed and dying of a cancer in the oral cavity and pharynx

Answer 16

diagnosed –> 1%

dying–> 0.3%

Question 17

carcinogenesis

Answer 17

• the accumulation of growth promoting mutation that results in cell transformation
• occurs in already existing (somatic cells) –> not passed down

Question 18

mechanisms of carcinogenesis

Answer 18

1. spontaneous gene or chromosome mutations
2. mutagens or radiation
3. tumor viruses (RNA and DNA)
4. inherited predisposition; “cancer families”

Question 19

RNA tumor viruses

Answer 19

RNA tumor viruses (oncogenic retroviruses) contain viral oncogenes derived from cellular proto-oncogenes capable of transforming cells

Question 20

DNA tumor viruses

Answer 20

• human papilloma virus (HPV) causes cervical cancer, oral caner
• epstein-barr virus (herpes 4) causes burkitt’s lymphoma or nasopharyngeal cancer
• human herpes virus 8 causes kaposi’s sarcoma

Question 21

DNA tumor viruses

Answer 21

• human papilloma virus (HPV) causes cervical cancer, oral caner
• epstein-barr virus (herpes 4) causes burkitt’s lymphoma or nasopharyngeal cancer
• human herpes virus 8 causes kaposi’s sarcoma

Question 22

genes that are mutated in cancer

Answer 22

1. proto-oncogenes
2. tumor suppressor genes
3. mutator genes

Question 23

proto-oncogenes

Answer 23

• gain of function mutations: covert proto-oncogenes to oncogenes (“activates them”)
• heterozygous
• ex: point mutations, deletions, gene amplification, chromosomal translocation
• genetic signature: limited number of mutations–> they are “drugable” (good targets for drug therapy)

Question 24

tumor suppressor genes

Answer 24

• loss of function mutations: tumor suppressor genes result in cell transformation
• homozygous
• genetic signature: large number of mutation–> potential target for gene therapy

Question 25

mutator genes

Answer 25

- loss of function mutations in enzymes involved in DNA replications and repair - enhance that rate of mutation accumulation - homozygous

Question 26

receptor tyrosine kinase signaling leads to

Answer 26

the activation of a transcription factors affecting growth and proliferation

Question 27

steps in receptor tyrosine kinase signaling

Answer 27

step 1: activation of receptor tyrosine kinase step2: activation of KRAS step3: activation of BRAF

Question 28

general structure of the receptor tyrosine kinase

Answer 28

- extracellular domain (variable--> to recognize different ligands) - little transmembrane domain - intracellular domain which is a tyrosine kinase (phosphorylates other proteins on tyrosine residues)

Question 29

step 1: what happens when the ligand binds to the extracellular portion?

Answer 29

you get a dimerization, then they cross phosphorylate each other

Question 30

mutational events that activate EGFR

Answer 30

activating point mutations or deletions cause ligand independent dimerization (activate receptor) --> lead to epidermal growth factor receptors over expression

Question 31

epidermal growth factor receptor tyrosine kinase inhibitors

Answer 31

- iressa: orally active EGFR tyrosine kinase inhibitor - traceva: used in lung and pancreatic cancer - caprelsa: used in medullary thyroid cancer

Question 32

step 2: activation of KRAS

Answer 32

- once you activate the receptor the next step is KRAS - KRAS is not an enzyme (not easily inhibited) - small GTP binding protein (active when bound to GTP) - bound to the membrane

Question 33

KRAS mutations

Answer 33

if you have these mutations you can get stuck in the active form of KRAS (pathways keeps going) - almost always caused by the same type of mutation on codon 12 or 13 - 20% of all tumors have a RAS mutation

Question 34

farnesyl trasnferase (FTase)

Answer 34

enzyme that helps in the anchoring of KRAS to the cell membrane inhibiting this enzyme would inhibit KRAS

Question 35

step 3: activation of BRAF

Answer 35

RAS bind to and activates BRAF - BRAF is an enzyme which means there are powerful inhibitors for this step - mutations in the kinase domain, V600E is a common kinase activator

Question 36

BRAF mutations in which cancers

Answer 36

-melanoma -colorectal carcinoma papillary thyroid carcinoma -some rare brain tumors

Question 37

philadelphia chromosome

Answer 37

- a piece of chromosome 9 switches with a piece of chromosome 22 - the new and shorter chromosome 22 contains abnormal BRC-Ab1 gene fusion - found in chronic myelogenous leukemia (CML) (95% carry this translocation) - gleevec is an effective treatment because it inhibits abnormal tyrosine kinase

Question 38

these lead to photo-oncogenes being converted to oncogenes

Answer 38

Activation of receptor tyrosine kinases (EGFR) KRAS activation BRAF activation Philadelphia chromosome - BCR-Abl tyrosine kinase