Ch 20: cancer

Question 1

Distinguish between different types of tumors and determine their tissue of origin

Answer 1

Carcinoma – from epithelial cells – most common
Myeloma, leukemia, lymphoma– from WBC and their precursors (hematopoietic cells)
Sarcoma – from connective tissue or muscle cells

Question 2

Describe the hallmarks of cancer

Answer 2

1. Altered homeostasis that results in cells growing and dividing at a faster rate than they die
2. Bypass of normal limits to cell proliferation
3. Evasion of cell-death signals
4. Altered cellular metabolism
5. Manipulation of the tissue environment for cell survival and to evade immune response
6. Escape of cells from their home tissues and proliferation in foreign sites (metastasis)

Question 3

Evidence for sequential accumulation of mutations

Answer 3

cataclysmic genome disruptions make genomes unstable, which makes it easier to accumulate mutations

aneuploidy
chromothripsis

Question 4

Difference between oncogenes and tumor-suppressor genes

Answer 4

Oncogene - gene that through the gain of function can promote cancer; generally dominant

Tumor-supressor gene- loss of function can promote cancer; generally recessive

Question 5

Mutations that lead to proto-oncogenes

Answer 5

Point mutation coding sequence–> hyperactive protein
Point mutation in regulatory site –> protein overproduction
Gene amplification –> protein overproduction
Chromosome rearragnement –> protein overproduction, hyperactive fusion proteins

Question 6

Difference between stem-cell and differentiated cell tumors

Answer 6

Stem – self-renewing cells present in many tissues. When stem cells divide, they can either become a terminally differentiated cell or remain a stem cell
Cancer stem – self-renewing cells found within tumors that can give rise to fresh tumors when implanted in different tissue/ organ

Question 7

Why do tumor cells have increased telomerase activity?

Answer 7

• can reactivate telomerase or evade death signals (ex p53)
• repair mechanisms

Question 8

What is genome instability?

Answer 8

an abnormally high rate of genetic changes occurring within a cell’s genome

Question 9

Examples of proto-oncogenes and tumor-suppressor genes

Answer 9

proto-onco: Myc, EGF receptor, src kinase
Supressor: , p53, Rb, Apc, Brca1, Brca2

Question 10

What mutations innactivate a tumor suppressor gene?

Answer 10

genetic silencing –> chromosome abnormalities, point mutations, deletions
epigenetic silencing –> methylation of the promoter irreversibly silencing the gene

Question 11

Why do colon polyps not necessarily become tumors?

Answer 11

Polyps develop from loss of Apc

Activation of K-ras, loss of Smad4, and loss of p53 are needed to become a tumor

Question 12

What is EMT and how does it contribute to cancer?

Answer 12

when epithelial cells lose their polarity and adhesiveness to take on mesenchymal phenotype and migratory behavior

Question 13

Cancer treatment approaches and their different efficacies

Answer 13

Generalized approach
Ionizing radiation and cytotoxic drugs: weakly selective, have detrimental side effects, can lead to secondary cancers

Targeted approach:
exploiting tumor’s genetic instability, target specific mutations to selectively kill cancer cells

Question 14

What do PARP inhibitors do?

Answer 14

kill cancer cells that have mutations in Brca1 and Brca2

Question 15

What does Gleevec (imatinib) do?

Answer 15

Inhibits oncogene Bcr-Abl, ultimately preventing leukemia

Question 16

How does injecting antibodies treat cancer?

Answer 16

• inhibit function of cancer cell proteins
• trastuzumab inhibits Her2

Her2 overexpresses breast cancers

Question 17

How can T cells be used as cancer treatment?

Answer 17

• CAR T therapy- collect patient’s T cells, engineer cancer-reactive population and reinfuse cells back to patient (augmenting T cell response to mutated cancer cells with neoantignets, which can be recognized as foreign)
• promoting T cell or dendritic cell infiltration into the tumor

Question 18

How can developing immune checkpoint inhibitors promote remission?

Answer 18

prevent tumors from binding inhibtory T-cell receptors (antibodies for PD1 or PDL1)

Promotes T cell or dendritic cell infiltration into the tumor

Question 19

Examples of how cancer cells can evolve to become resistant to therapies

Answer 19

resistance to PARP inhibitors due to reactivation of Brca gene

small group of cancer stem cells remains and continutes to proliferate

Question 20

multidrug resistance

Answer 20

upregulation of gene Mdr1 or Abcb1-ABC transporters that pump lipophilic drugs out of the cells to prevent intracellular accumulation of cytotoxic anti-cancer drugs

Question 21

What is a neoplasm?

Answer 21

• tumor
• a swelling of a part of the body, without inflammation, caused by an abnormal growth of tissue.
• A new and abnormal growth of tissue in some part of the
  body

Question 22

What 2 properties define cancer cells?

Answer 22

1. Reproduction beyond the normal restraints on cell growth and division
2. Invasion and colonization of territories normally reserved
   for other cells

Question 23

Primary tumor

Answer 23

• the original cell in tissue that gave rise to the tumor
• Can be traced back even after metastasis
• arises in a specific organ

Question 24

which mutations can be passed down to progeny?

Answer 24

Germline
NOT somatic

Question 25

Aneuploidy

Answer 25

gain or loss of individual chromosomes (uneven split) during
mitosis as result of both sister
chromatid attachment to the same pole

Question 26

Chromothripsis

Answer 26

DNA damage and chromosomal rearrangement resulting from isolation of chromosome in a micronucleus

Question 27

contact inhibition

Answer 27

when a cell touches nother cell, stops dividing. But cancer cells lose ability to respond to these signals and ignore them and continue dividing

Question 28

Warburg effect

Answer 28

abnormally high glucose uptake that allows tumors to be imaged in whole-body scans

Question 29

How do cancer cells gain energy?

Answer 29

glycolysis, not oxidative phosphorylation (so removing oxygen is not enough because not required for glycolysis)

Question 30

Stroma

Answer 30

• connective tissue that surround the tumor containing fibroblasts, inflammatory white blood cells, blood vessel cells
• they are not cancer cells
• Cancer cells induce modifications of the ECM, modifying immune response and promoting angiogenesis

Question 31

Metastasis

Answer 31

formation of secondary tumors invading other sites of the body
Steps:
1. Break free from the primary tumor
2. Enter the circulatory system
3. Exit the circulatory system at another
location
4. Form colonies of cells in the distant organ

Question 32

Rb
Ras
p53

Answer 32

Rb: cell-cycle entry
Ras: signaling cascade that drives growth
p53: tolerance to stress and DNA damage