L1 - L3 Flashcards
The hallmarks of cancer
A method for organizing the characteristic properties and complexities of cancer
Growth signal autonomy
The ability to grow without requiring external growth signals
Evasion of growth inhibitory signals
cells become unresponsive to inhibitory growth signals
avoiding the immune system
Cells produce methods of avoiding detection of the immune system and continue to proliferate
Unlimited replicative potential
ability to replicate and ignore telomere shortening or invoking unregulated telomerase activity
Tumor-promoting inflammation
tumor growth as a result of inflammation via an increase in growth signaling that stimulate tumor cells
invasion and metastasis
cell acquire an ability to migrate and invade other regions of the body
angiogenesis
growth and attraction of blood vessels to tumors
genome instability and mutation
DNA damage and mutations cause phenotypic changes in cells
Evasion of cell death
cells avoid apoptotic mechanisms
reprogramming of energy metabolism
cancer cells exhibit an alternative metabolic profile compared to normal cells
Unlocking phenotypic plasticity
Cells change their phenotype depending on the micro-environment that they are in
Senescent cells
metabolically active cells that cannot replicate but posses tumor promoting factors
polymorphic microbiomes
tumor specific bacteria or bacteria that can promote tumors or cancers via the toxins they produce or mechanisms that exploit
Non-mutational epigenetic changes
changes to the cells that do not impact the sequence of the DNA
Genome
A complete set of genetic material in an organism
most carcinogens
cause alterations to the DNA sequence
Accumulation of mutations over time
results in a multi-step process that underlies carcinogenesis or increased risk of cancer with age
mutation burst
a single catastrophic event in a cell that leads to many mutations and cause cancer
changes in the epigenome
result in altered gene expression
Extrachromosomal DNA
DNA not included in the chromosome may play a role in cancer development
Alterations in the genome cause
altered cell growth, death, and differentiation, and affects the cell number in a tissue
Oncogenes role in cancer
upregulated in a single allele (dominant) resulting in unregulated cell growth and division
I. Tumor suppressor genes roles in cancer
Down-regulated (recessive) loss of an inhibitor leading to abnormal growth
II. Tumor suppressor genes roles in cancer
Down-regulated (lower gene dose) of a protein or product involved in the maintenance of regulatory mechanisms in the cell
cancer as a systemic disease
not a cell-autonomous process; depends on interactions between cells and tumor microenvironment; cell have ability to invade other parts of the body
influential factors in human carcinogenesis
Age, Environment, Reproduction, Diet, Exercise, Alcohol, Smoking
Principles of conventional cancer therapies
Surgery is not precise; Chem and radio can eradicate and inhibit metastasized cells
Disadvantages of conventional cancer therapies
often severe and debilitating and non-specific
Aim of all therapies
are to achieve effective result while minimizing side effects
therapeutic index
difference between the maximum tolerated dose and the minimum effective dose
Centromeres are
required for cell division
Aneuploidy
multiple copies of the same chromosome; having an abnormal amount of chromosome pairs in the cell
Cancer cells often show
structural chromosome changes (can be visualized using mFISH)
Mutations in the regulatory region
may affect gene expression
mutations in the coding region
may affect the product
Promoter region
Upstream of transcription site; where RNA Pol II and TF bind
transition mutation
purine to purine; or pyrimidine to pyrimidine
transversion
purine to pyrimidine
insertion
addition of a base into the DNA; affects the ORF
Deletion
deletion of a base into the DNA; affects the ORF
Insertions/deletions in multiples of three
loss or gain of an amino acid; ORF is not changed
insertions and deletions in multiples of three
often results in termination of transcription (results in a stop codon); frame shift
Deletions to large amounts of base pairs
exon loss; parts of a protein/product are missing leading to degradation
promoter loss; no expression
Chromosomal mutations can include
severe aberrations, multilocus deletions, translocations
chromosomal translocations
these occur when chromosomes break and the resulting fragments reattach to different chromosomes
Balanced translocation
the exchange of genetic material between two nonhomologous chromosomes
