Cancer Flashcards
what is cancer?
uncontrolled cell division; a collection of disorders that share two properties: cell reproduction and division despite various restraints and controls AND invasion
what is a neoplasm?
mass of cells or tumor; if benign, then there is no invasion
what does malignant mean? what are they made of?
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”
what does it mean to metastasize?
If malignant and invasive, the cells metastasize (spread) to more distant sites in the body to form secondary tumors
list 8 cell constraints
growth/death signals, Genetic or chromosomal issues, Cell-cell interactions, Adhesion molecules, Differentiation, Growth and cell division, Migration, Cell Death
what is a carcinoma? an adenoma?
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
what’s a sarcoma?
cancers arising from connective tissue or muscle cells
what’s lymphoma/leukemia?
cancers arising from white blood cells and immature precursors proliferate
what is the basic cause of cancer?
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
what is another cause of cancer besides mutations?
genetic alterations of specific molecules such as integrins OR chromosome issues
what are the 5 mutations required for onset of clinically observable tumors?
- 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
what are tumors comprised of?
Tumors are comprised of genetically identical cells and are “clonal” in nature; a single aberrant cell starts it all
what does clonal expansion mean? what can happen after this?
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
how do cancer cells avoid replicative senescence?
through p53 mutation or telomerase maintenance
why must cancer cells survive in a foreign environment?
bc of metastasis
How do tumors induce angiogenesis? what happens after?
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
what are the three categories of cancer-critical genes?
- Proto-oncogenes/oncogenes
- Tumor suppressor genes
- DNA maintenance genes
what are proto-oncogenes? how are these activated? what can it be compared to?
necessary for normal cellular proliferation; originally obtained from viruses; Proto-oncogenes can become “activated” typically by point mutation to become oncogenes; accelerator
what are oncogenes? what happens when these are activated?
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
what do tumor suppressor genes do? what happens when there’s a mutation present here? what are they aka?
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
what is p53? aka?
p53 is a cellular stress sensor that reacts to various stresses and produces specific responses that stops damaged cells from dividing
why is p53 known as the guardian of the genome?
Tumor suppressor gene, DNA repair gene; Only functions in certain circumstances, limiting the harm done by DNA damage
what are 3 functions of p53?
Can set apoptosis in motion
Stops cell division and cell cycle
Induces transcription of p21
loss of p53 promotes cancer, list 4 ways it can do this
Allowing DNA-damaged cells to divide
Allows damaged cells to escape apoptosis
Leads to genetic instability
Makes cells resistant to anti-cancer drugs
what are DNA repair genes? what happens if these are mutated?
those that assure accurate replication of DNA; p53 is good example of this; if mutated, can cause genomic instability (widespread mutations, chromosome breaks, aneuploidy)
how does p53 lose its function? what happens then?
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
what is an example of a type of protein coded for by tumor suppressor genes? what do these do?
cyclin-dependent kinase inhibitors; these proteins inactivate cyclin-dependent kinases and prevent them from phosphorylating, thereby controlling cell cycle
how do tumor cells overcome replicative cell senescence?
by activating telomerase which replaces the telomere segments that are lost during each cell division
what is replicative cell senescence?
cell death after a specific number of cell divisions
what is precision medicine?
using individual’s genome and proteome to treat cancer
what is the difference bw cyostatic and cytotoxic?
blocks cell proliferation; kills tumor cells
how can drug targets be identified? give examples of each of the 3
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)
when is targeted therapy used? give 5 examples
if chemo does not work; Hormone therapies; signal transduction inhibitors; gene expression modulators; apoptosis inducers; angiogenesis inhibitors; immunotherapy
