Moss - Cancer Flashcards
what is cancer?
cancer is fundamentally a genetic disease, and tumors develop through a process that resembles evolution and natural selection
how are cancer cells able to form?
cancer cells escape the normal growth controls on somatic cells and may compete with their neighbors for blood supply and space
they may move from their origins and grow elsewhere in the body
why are cancers likely to form more often than we are aware?
only a few tumors grow enough of be noticed and a subset of these may become dangerous
what are the different types of cancer?
neoplasm
benign tumor
malignant tumor
metastases
what is a neoplasm?
a tumor
a growing mass of abnormal cells
what is a benign tumor?
a tumor that remains a single mass, may be possible to remove by surgery
what is a malignant tumor?
a cancer
a tumor that can invade tissues
what is metastases?
secondary tumors that are the result of spreading of the primary tumor
not possible to remove by surgery alone
must use chemotherapy, radiation, or a combo of the three
tumor established at new site
what do tumors consume an abundance of?
glucose
what are tumors classified by?
their tissue of origin
what are the types of tumors that can be malignant?
carcinomas
sarcomas
leukemias
tumors of the nervous system
how many types of cancer are there?
more than 200
how many organs in your body can develop cancer?
more than 60
what is a carcinoma?
cancers arising from epithelial cells, about 90% of all tumors
what are sarcomas?
cancers arising from muscle cells, fat cells, bone, and blood vessels, or connective tissue
what are leukemias?
cancers arising from hematopoietic (blood) cells
why are about 90% of all tumors carcinomas/epithelial in origin?
they are the most rapidly turning over cells
what is the difference between a benign tumor and malignant tumor?
- benign:
- can be removed
- contained within basal lamina
- malignant tumor
- break through the basal lamina and leak out
what can a primary malignant tumor do?
metastasize to another organ
what do the characteristics of a particular cancer reflect?
their cells of origin
what cancers easily metastasize?
melanomas
what can metastases of melanomas look like?
they may be pigmented like the melanocytes
how do melanocytes develop?
from migrating neural crest cells
what must happen for cancer to form?
mutations must occur in proliferating cells
TRUE or FALSE: Terminally differentiated cells are not likely to form tumors.
TRUE
what is the estimated number of cell divisions in the life of an inidivual?
1016
what contributes to cancer development
spontaneous mutation rate
what is the average spontaneous mutation rate?
10-6 per cell division
this is the rate without any environmental causes
what is likely to have happened to every single gene?
every single gene is likely to have acquired a mutation on more than 109 separate occasions in one cell or another
why doesn’t cancer occur more frequently?
it is hard for a mutant cell to become cancer because the body has preventative mechanisms to detect and stop it
what is cancer incidence a function of?
age
the curve is sigmoidal
TRUE or FALSE: A single mutation is not enough to cause a cancer
TRUE
what is one piece of evidence that more than one mutation is needed to create a cancerous cell?
Cancer incidence increases with age
what do cancers require to be malignant?
multiple genetic changes
perhaps 10 or more
how do cancers develop?
gradually from increasingly aberrant cells
TRUE or FALSE: Cancer may not appear until long after exposure to causative agent.
TRUE
how long can cancer develop after occupational exposure to asbestos? what kind?
30-50 years
mesothelioma
how long can cancer develop after heavy smoking? what kind?
10-20 years
lung cancer
how long can cancer develop after atomic bombs at Hiroshima and Nagaskai? what kind?
5 years
leukemias
what must happen to cancer cells to progress?
they must accumulate somatic mutations
how can mutations occur?
may occur due to the inherent error rate of copying DNA as cells divide
may run in families
Increased exposure to agents that cause mutations
what causes genetic instability in cancers?
point mutations
small insertions and deletions
chromosomal rearrangements
chromosomal translocations
duplications or deletions of while chromosomes (aneuploidy)
what factors contribute to the genetic instability in cancers?
defects in DNA replication
defects i DNA repair
defects in cell-cycle checkpoints
errors in mitosis
what do DNA maintenance genes do?
they affect DNA repair, fidelity of replication, chromosome alignment during mitosis, and chromosome stability
what happens if a cell has a mutation in DNA maintenance genes?
cancers can develop
what are DNA maintenance genes that people tend to have mutations in?
BRCA½
what is the mutation rate in some cancer cells?
10-20 times the mutation orate of normal cells
Cancer cells are characteristically…
genetically unstable
what can be used to show the chromosomal abnormalities of cancers?
karyotyping
what does tumor progression involve?
successive rounds of mutation and selection
TRUE or FALSE: in cancer cells, each mutation increases chance of more mutations to to occur
TRUE
what does sequencing more than 10,000 genes in a set of breast and colorectal cancers reveal?
that cancer cells have accumulated enough mutations to cause an amino acid change in the proteins of roughly 100 genes
what does a subset of genes found to be repeatedly mutated in a particular type of cancer suggest?
that alterations in as many as 20 genes are needed to drive tumor progression
what can cancer critical mutations cause?
increase rate of division
disables programmed cell death (apoptosis/autophagy)
decrease propensity for differentiation
prevent senescence due to stress and damage
affect any of the other characteristics of cancer cells
what are the characteristics of cancer cells?
- reduced dependence on signals from other cells for survival growth and division
- increased tolerance for stress and internal derangement
- indefinite proliferation
- genetic instability
- increased invasiveness
- High need for nutrients
- survival and proliferation in abnormal locations
- ability to modify surrounding tissues
- escape from immune surveillance
what does it mean that cancer cells have reduced dependence on signals from other cells for survival, growth, and division?
mutations activate these pathways inappropriately
what does it mean that cancer cells have increased tolerance for stress and internal derangement?
the pathways for apoptosis are almost always defective
what does it mean that cancer cells have indefinite proliferation?
normal cell shave limitations on the number of divisions thy undergo (cell senescence due to telomere shortening)
cancer cells don’t
what does it mean that cancer cells have genetic instability?
once DNA repair mechanisms are damaged, mutations become more frequent
what does it mean that cancer cells have increased invasiveness?
The loss of cadherins and other adherence molecules and the signals that they generate allows them to move
what does it mean that cancer cells have high need for nutrients?
Cancer cells use glycolysis over OxPhos to make ATP
this is less efficient, but can work in oxygen-deprived tumor microenvironments
what does it mean that cancer cells have survival and proliferation in abnormal locations?
the independence on extracellular signals and the lack of apoptosis remove the primary barriers from growth out of place
what does it mean that cancer cells have ability to modify surrounding tissues?
Highly progressed cancers can remodel surrounding tissues and cause non-tumor cells to further support the tumor’s growth
uses blood vessels and growth factors as collaborators
what does it mean that cancer cells escape from immune surveillance?
The immune system requires certain molecular markers to recognize and destroy aberrant cells, markers that the tumor cells suppress or eliminate
they are no longer recognized as aberrant cells
what does cancerous growth often depend on?
defective control of cell death, cell differentiation, or both
what do cancer-critical genes regulate?
cell proliferation
cell growth
DNA repair
cell death and survival
as well as other processes like (apoptosis, immune response, regulation of gene expression
what are cancer critical genes?
mutated genes that continuously occur
not necessarily cancer causing
what are oncogenes?
genes that actively cause cancer, usually a mutant form, genetically dominant (hundreds of different oncogenes)
what are protoncogenes?
genes that when mutated can become oncogenes
not necessarily cancer
what are tumor suppressor genes?
genes whose absence causes cancer
they normally prevent the formation of a cancer
genetically recessive
p53
what are examples of genes whose function or expression is altered in cancers?
DNA repair genes
cell death genes
differentiation genes
cell cycle regulators
microRNAs
immune system function genes
what are examples of cancer critical genes?
oncogenes
protooncogenes
tumor suppressor genes
what mutated cancer gene is a dominant (gain-of-function) mutation?
oncogene
activating mutation enables oncogene to stimulate cell survival, proliferation, or both
what mutated cancer gene is recessive (loss-of-function)
tumor suppressor
two activating mutations functionally eliminate the tumor suppressor gene, promoting cell survival, and proliferation
what are the different ways to activate oncogenes?
mutation in coding sequence
gene amplification
chromosome rearrangement
what is heterozygosity?
the possession of two different alleles of a particular gene or genes by an individual
what is loss of heterozygosity (LOH)?
a cross chromosomal event that results in loss of the entire gene and the surrounding chromosomal region
what are the different ways a tumor suppressor could be inactivated?
heterozygosity
loss-of-heterozygosity
what are the possible ways of eliminating Rb Gene?
nondisjunction, causing chromosome loss
chromosome loss, then duplication
mitotic recombination
gene conversion
deletion
point mutation
what happens if a healthy cell with only one normal Rb gene copy is mutated?
mutation of single healthy copy can cause total loss of healthy genes
what is the important of APC to the inhibition of Wnt signaling?
when Wnt is off, the APC complex is active and Beta-catenin is degraded
(APC inhibits Wnt pathway)
when Wnt is on, APC complex is inactive and Beta-omega-catenin is released
(no APC Wnt pathway is overactive)
what is familial adenomatous polyposis coli?
an inherited disease that predisposes someone to colon cancer
issue with APC gene
how do colorectal cancers evolve?
slowly via succession of visible changes
what is the progression from normal cell to metastasis?
what can the steps of tumor progression often be correlated with?
specific mutations
how is each case of cancer characterized?
by its own array of genetic lesions
what do some colorectal cancers have defects in?
DNA mismatch repair
what is a primary tumor?
the original tumor that gives rise to metastases
when is a primary tumor normally detected?
usually not detected until it contains 109 cells
what may be associated with a primary tumor?
non-cancerous cells like fibroblasts and blood vessels
who discovered the Philadelphia Chromosome in CML?
Peter C. Nowell
David A. Hungerford
how do we know tumors arise from single cells?
because they can have unusual mutations
if all the cancer cells share the same unusual mutation…
they are very likely to be a clone
what is the Philadelphia Chromosome Translocation?
found in patients with Chronic Myelogenous Leukemia (CML)
it is a translocation between chromosomes 9 and 22
what do casual genetic changes in cancers mean?
they are more subtle and indicate clonal origin on most clonl
what is the molecular result of the translocation of the Philadelphia Chromsome?
the generation of the Bcr-Abl fusion protein
what is BCR-Abl?
it resembles Abl and Src
its primary cancer-causing feature is its unregulated expression
what is Gleevec?
treatment for several tumors
development of the drug was dependent on a deep understanding of the molecular biology underlying the disease
what can small molecules be designed to do?
inhibit specific oncogenic proteins
How does Gleevex affect the action of Bcr-Abl and othert kinases?
what is Gleevec effective against?
leukemias
melanoma
certain sarcomas
what do immunotherapies that targetT cells do?
immunotherapies that target inhibitory regulation of T cells such as anti-PDI antibodies can cure otherwise incurable cancers
what do anti-immune-checkpoint antibodies do?
they disinhibit cytotoxic T cells that recognize novel parts of proteins on cancer cells
what does treatment with a monoclonal antibody (ipilimumab) on a patient with advanced metastatic melonoma do?
it binds the T cell protein CTLA-4
after 16 weeks, the tumors were smaller
by 72 weeks, they had essentially been eliminated
