Cancer

Question 1

Cells of multicellular organism

• Self-sacrifice is the rule
• Committed to collaboration
• To coordinate their behavior, the cells send, receive, and interpret an elaborate set of extracellular signals that serve as social controls, directing cells how to act

Question 2

Healthy cell (rest to die)

Answer 2

Rest -> Grow -> Divide -> Differentiate -. Die

Question 3

cells divide repeatedly out of control even though they are not needed (failure of cellular regulation)

Answer 3

Cancer

Question 4

cancerous cells

• Nucleus that is larger and darker than normal
• Abnormal number of chromosomes arranged in a disorganized fashion
• Cluster of cells without a boundary
• Small cytoplasm
• Multiple nuclei
• Multiple and large nucleoli
• Coarse chromatin

Question 5

Key players in cancer

Answer 5

Proto-oncogenes
* normally activates cell division
* growth factor genes become oncogenes (cancer-causing) when mutated
* if switched “ON” can cause cancer
* example: RAS (activates cyclins), MYC, EGFR

Question 6

Key Genetic Players in Cancer

Answer 6

1. Tumor suppressor genes
   * Loss of function
   * E.g. PTEN
   * Tumor suppressor gene that regulates cell growth, proliferation and apoptosis by inhibiting the P13K/AKT/mTOR signaling pathway
2. Genome maintenance genes
   * BRCA1/2
   * Homologous recombination, checkpoint control
   * Associated with hereditary breast and ovarian cancer

Question 7

Hallmarks of Cancer

Answer 7

1. Resist cell death
2. Sustain proliferative signaling
3. Evade growth suppressors
4. Induce angiogenesis
5. Enable replicative immortality
6. Activate invasion and metastasis

Question 8

• process by which normal somatic cells reach an irreversible stage of cell cycle arrest following multiple rounds of replication; this end stage is associated with marked changes in gene expression and function.

Answer 8

Replicative senescence

Question 9

Oncogenic Signaling Pathways

Answer 9

• RTK/RAS/RAF/MEF?ERK pathway
• Promotes proliferation
• P13K/AKT/mTOR pathways
• Promotes survival and growth
• WNT/ẞ-catenin pathways
• Regulates cell fate, stemness
• Oncogenic mutations often cause ligand-independent activation, receptor amplification, or GTPase inactivation

Question 10

Cancer & Checkpoint control

• Cancer is essentially a failure of cell division control
• What control is lost?

Answer 10

lose checkpoint stops

Question 11

Cancer & Cell Growth
* ______ halts cell division if it detects damaged DNA
* stimulates repair enzymes to fix DNA
* forces cell into G0 resting stage
* keeps cell in G1arrest
* causes apoptosis of damaged cell
*ALL cancers have to shut down — activity

Answer 11

p53 protein

Question 12

“Go-ahead” signals
* Primary mechanism of control is through _______
* kinase enzymes either activates or inactivates cell signals
* E.g. loss of function of p16 leading overproduction of ________

Answer 12

phosphorylation; cyclin D

Question 13

Evasion of Apoptosis

Answer 13

• Inactivation of p53
• Impaired mitochondrial outer membrane permeabilization
• Cancer can produce BcL-2 or protein which mimics Bcl-2 (inhibits apoptosis)

Question 14

Apoptosis and cancer
* Inhibit expression of the gene for Apaf-1
* Blocks the T-cells’ FasL, or kill cytotoxic T cells with FasL

Question 15

• Invasion/migration into new tissues, establishing secondary areas of proliferation

Answer 15

Metastatis

Question 16

Mass of abnormal cells

Answer 16

Tumor

Question 17

• abnormal cells remain at original site as a lump, held together by cell adhesion molecules
• p53 has halted cell divisions

Answer 17

Benign tumor

Question 18

• cells leave original site
• lose attachment to nearby cells
• carried by blood & lymph system to other tissues
• start more tumors = metastasis

Answer 18

Malignant tumor (cancer)

Question 19

Metastasis
* To metastasize the cell must alter its cell adhesion molecules and degrade the extracellular matrix and basal lamina (epithelial-to mesenchymal transition)
* ____and ______ are some of the proteins secreted by cancer cells to degrade the ECM

Answer 19

MMP (matrix metalloproteinase); plasminogen activator

Question 20

• Tumor growth requires formation of new blood vessels

Answer 20

Angiogenesis

Question 21

Steps of angiogenesis

Answer 21

• Degradation of basal lamina that surrounds the capillary
• Migration of endothelial cells
• Division of endothelial cells
• Formation of new basement membrane

Question 22

Makes rapid tumor growth possible by supplying oxygen and nutrients and removing waste

Facilitates metastasis

Answer 22

Neovascularization

Question 23

Angiogenesis
* Growth factors (angiogenic properties):

Answer 23

*Basic fibroblast growth factor
* Transforming growth factor α
* Vascular endothelial growth factor (VEGF)

Question 24

Cancer has altered metabolism
* Increased glucose uptake and preferential production of lactate, even in the presence of oxygen (called __________)
* Lifestyle plays a role in cancer prevention

Answer 24

Warburg effect

Question 25

Some cells are able to produce their own growth factor to stimulate their own growth, this is called_________

Answer 25

Autocrine stimulation

Question 26

Growth factor expressed by glioblastomas

Answer 26

PDGF

Question 27

Growth factors expressed by sarcomas

Answer 27

TGF-α and EGFR

Question 28

EGF receptors are found in:

Answer 28

Skin Breast Colon Lung

Question 29

EGF receptor's role:

Answer 29

Regulation of: - Cell proliferation - Differentiation - Survival

Question 30

Overexpressed EGFR arised from:

Answer 30

Colon Rectum Head Neck

Question 31

a chimeric antibody that binds directly to the epidermal growth factor receptors and competitively inhibits the binding of TGF and other ligands

Answer 31

Cetuximab