Cancer

Question 1

what is cancer?

Answer 1

uncontrolled cell division; a collection of disorders that share two properties: cell reproduction and division despite various restraints and controls AND invasion

Question 2

what is a neoplasm?

Answer 2

mass of cells or tumor; if benign, then there is no invasion

Question 3

what does malignant mean? what are they made of?

Answer 3

neoplasms invade nearby tissues; Malignant neoplasms are made up of cells from a single ancestor; they are monoclonal in origin and form the “primary tumor”

Question 4

what does it mean to metastasize?

Answer 4

If malignant and invasive, the cells metastasize (spread) to more distant sites in the body to form secondary tumors

Question 5

list 8 cell constraints

Answer 5

growth/death signals, Genetic or chromosomal issues, Cell-cell interactions, Adhesion molecules, Differentiation, Growth and cell division, Migration, Cell Death

Question 6

what is a carcinoma? an adenoma?

Answer 6

cancers arising from epithelial cells (Most of our cells are these so 80% of cancers are these); a benign tumor arising from epithelial cells in a gland

Question 7

what’s a sarcoma?

Answer 7

cancers arising from connective tissue or muscle cells

Question 8

what’s lymphoma/leukemia?

Answer 8

cancers arising from white blood cells and immature precursors proliferate

Question 9

what is the basic cause of cancer?

Answer 9

damage to specific genes (mutations) that accumulate in somatic cells (somatic mutations) over time until a cell loses a critical number of growth-controlled mechanisms and initiates a tumor

Question 10

what is another cause of cancer besides mutations?

Answer 10

genetic alterations of specific molecules such as integrins OR chromosome issues

Question 11

what are the 5 mutations required for onset of clinically observable tumors?

Answer 11

• Gene amplification: extra copies of a single gene are transcribed
• Nonsense mutations
• Gene deletion: loss of a sequence of nucleotides within an exon or splice site
• Gene rearrangements: in Ig-producing cells (T and B) can produce massive clonal populations
• Point mutations: replacement of a single nucleotide

Question 12

what are tumors comprised of?

Answer 12

Tumors are comprised of genetically identical cells and are “clonal” in nature; a single aberrant cell starts it all

Question 13

what does clonal expansion mean? what can happen after this?

Answer 13

Alterations in cellular DNA accumulate over time in succeeding generations of daughter cells; daughter cells with several mutations replace the cells previously comprising the tumor

Question 14

how do cancer cells avoid replicative senescence?

Answer 14

through p53 mutation or telomerase maintenance

Question 15

why must cancer cells survive in a foreign environment?

Answer 15

bc of metastasis

Question 16

How do tumors induce angiogenesis? what happens after?

Answer 16

cell aggregates need oxygen to survive without oxygen, hypoxia sets in; Hypoxia activates an angiogenic switch that increases Hypoxia-inducible Factor (a gene regulatory protein) that activates transcription of genes that encode proteins that attract endothelial cells (via VEGF) and formation of new blood vessels; tumors function this way

Question 17

what are the three categories of cancer-critical genes?

Answer 17

• Proto-oncogenes/oncogenes
• Tumor suppressor genes
• DNA maintenance genes

Question 18

what are proto-oncogenes? how are these activated? what can it be compared to?

Answer 18

necessary for normal cellular proliferation; originally obtained from viruses; Proto-oncogenes can become “activated” typically by point mutation to become oncogenes; accelerator

Question 19

what are oncogenes? what happens when these are activated?

Answer 19

originate from proto-oncogenes that encode protein products that control cell growth and differentiation; When activated by mutation, these act as dominant gain-of-function mutations that lead to the deregulation of cell cycle control; a growth-promoting effect

Question 20

what do tumor suppressor genes do? what happens when there’s a mutation present here? what are they aka?

Answer 20

Encode for protein products that suppress tumor formation by controlling cell growth;  Loss-of-function mutations result in inactivation of the tumor suppressor protein and can lead to uncontrolled cellular proliferation; brakes

Question 21

what is p53? aka?

Answer 21

p53 is a cellular stress sensor that reacts to various stresses and produces specific responses that stops damaged cells from dividing

Question 22

why is p53 known as the guardian of the genome?

Answer 22

Tumor suppressor gene, DNA repair gene; Only functions in certain circumstances, limiting the harm done by DNA damage

Question 23

what are 3 functions of p53?

Answer 23

Can set apoptosis in motion
Stops cell division and cell cycle
Induces transcription of p21

Question 24

loss of p53 promotes cancer, list 4 ways it can do this

Answer 24

Allowing DNA-damaged cells to divide
Allows damaged cells to escape apoptosis
Leads to genetic instability
Makes cells resistant to anti-cancer drugs

Question 25

what are DNA repair genes? what happens if these are mutated?

Answer 25

those that assure accurate replication of DNA; p53 is good example of this; if mutated, can cause genomic instability (widespread mutations, chromosome breaks, aneuploidy)

Question 26

how does p53 lose its function? what happens then?

Answer 26

Inactivation of these genes occurs through mutation or deletion of sequences over a large coding region (exon); causes uncontrolled cellular proliferation because of loss of negative regulation

Question 27

what is an example of a type of protein coded for by tumor suppressor genes? what do these do?

Answer 27

cyclin-dependent kinase inhibitors; these proteins inactivate cyclin-dependent kinases and prevent them from phosphorylating, thereby controlling cell cycle

Question 28

how do tumor cells overcome replicative cell senescence?

Answer 28

by activating telomerase which replaces the telomere segments that are lost during each cell division

Question 29

what is replicative cell senescence?

Answer 29

cell death after a specific number of cell divisions

Question 30

what is precision medicine?

Answer 30

using individual’s genome and proteome to treat cancer

Question 31

what is the difference bw cyostatic and cytotoxic?

Answer 31

blocks cell proliferation; kills tumor cells

Question 32

how can drug targets be identified? give examples of each of the 3

Answer 32

growth or survival proteins present in greater abundance in cancer cells (HER-2); Altered proteins that drive cancer progression (BRAF is a cell growth protein, but BRAFV600E is altered); Chromosomal abnormalities in cancer cells (fusion protein production such as BCR-ABL)

Question 33

when is targeted therapy used? give 5 examples

Answer 33

if chemo does not work; Hormone therapies; signal transduction inhibitors; gene expression modulators; apoptosis inducers; angiogenesis inhibitors; immunotherapy