cancer Flashcards
Cancer
abnormal cells divide in accelerated/uncontrolled manner AND have potential to invade other tissues
Benign
non-cancerous
lack ability to spread into neighboring tissues
Malignant
cells divide uncontrollably and at abnormally fast and INVADE neighbors
aka cancerous tumors
Metastasis
spread of CA from one tissues to another
6 hallmarks of CA
Evading growth suppressors activating invasion and metastases Enabling replicative immortality inducing angiogenesis resisting cell death sustaining proliferative signaling
Evading apoptosis
Normal cells are signaled to die with damage
CA cell can evade this: allows damaged cells to continue replicating
genetic factors may be involved
p53 tumor suppressor gene
Self0sufficiency in growth signals
normal cells require external growth factors in order to grow and proliferate
CA cell do NOT, they produce them on their own
can bypass check points
Insensitivity to Anti-growth Signal
Normal cel proliferation is regulated and kept under control by antigrowth signal, no more basement membrane–stop growth.
CA are insensitive to antigrowth signals, will grow on top of each other
this is evident even in vitro
tissue invasion and metastasis
cancer cells must be able to metastasize or invade new tissues
tumors send “pioneer cell” to invade adjacent tissue
pioneer cells must first interact normally with existing normal local cells
pioneer cells then recruit cells from local tissue to make mew tumors
limitless replicative potential
normal cells can only divide a certain number of times before they die: telomere length determines the number of times a cell can divide, it shortens after each division until no more left and stops dividing
Telomearase maintain telomeres length: is UPREGULATED in CA
CA cells can divide infinitely, but the often pick up DNA errors due to increased in frequency of cell division
p53 tumor suppressor gene plays a role in limiting replication: TURNED OFF in CA
Sustained Angiogenesis
the formation of new blood vessels
tumors need a blood supply to be able to grow in size and spread
angiogenesis also provides the tumors the o2 and nutrients it needs to grow
tumor suppressor
a gene that protects a cell from becoming CA
generally loss-of-function nutation in these genes cause cells to become susceptible to becoming CA
Oncogene
a gene that puts a cell on the path to becoming CA
begin as proto-oncogenes which have regular physiological function in the cell (mostly relating to proliferation and differentiation)
begin to over express, thereby becoming oncogenes
proto-oncogenes mutate and becomes oncogenes
tumor suppressor p53
classic role: prevents cells with DNA damage from dividing and proliferating
know as “guardian of the genome”
about 50% of CA have p53 mutations
in CA p53 is permanently OFF
two-hit hypothesis
for why tumor suppressor genes become insufficient to prevent CA
basically states that both alleles for a tumor suppressor gene must be mutated in order for the gene to lose function
not universally true but stands for the majority of tumor suppressor genes
*need 2 mutations
interfering with DNA synthesis
folate must be taken up by the cell and reduced at FH2 then FH4 by dihydrofolate reductase in order to produce nucleosides
Methotrexate
has a higher affinity for dihydrofolate reductase than does FH2, thereby preventing its reduction to FH4
bind to dihydrofolate so FH2 can’t make nucleosides
Doxorubicin
Cytotoxic antibiotic
topoisomerase II opens ups DNA and this drug:
prevents the DNA strand from being put back together, thereby inhibiting DNA replication: therefore the cell can’t divide
Topoisomerase II
relaxed the DNA supercoil and breaks the strand for replication
Cyclophosphamide
Alkylating agents prevent replication of DNA attach alkyl groups to guanines causes guanines on the helix to crosslink, thereby making DNA "stuck" in its supercoil (covalent bond, so can straighten out and copy machinery can do its job and replicate) if DNA cannot uncoil, it can't replicate
Vincristine
interfering with mitosis
binds to microtubules dimers, preventing polymerization of dimers
arrest the cell in metaphase
can’t get into 2 cells
New targeted therapies
hormone therapy
monoclonal antibodies
tyrosine kinase inhibitors
tamoxifen
hormone therapy
for Tx estrogen receptor positive breast CA
antagonist at the estrogen receptor
in ER positive breast CA estrogen is necessary for cell proliferation
bind to receptor so estrogen can’t so then never get signal to divide
monoclonal antibodies
block growth signals
stop new blood vessels from forming
cetuximab
block growth signals
binds to mutated growth factor receptor and prevents its downstream signaling
but not all hyper-proliferation is caused by mutated EGFR (external), may be caused by nutated downstream effectors of EGFR–in this case cetuximab would NOT work, only effects GF receptor
Bevacizumab
trade name: avastin
anti-angiogenic
monoclonal antibody that blocks angiogenesis
inhibits vascular endothelial growth factor-A
without vascularization, tumors cannot survive
binds to receptor prevents GF from binding and tumor won’t survive
tyrosine kinase
tyrosine kinase an enzymes that removes a phosphate group from ATP and attaches it to a protein onto a tyrosine amino acid
the addition of a kinase to a protein generally starts a signaling cascade that can lead to cell proliferation
tyrosine kinase inhibitors:
somehow prevent the phosphorylation of the tyrosine kinase target
Philadelphia chromosome
also known as Philadelphia translocation
occurs when chromosome 22 has a specific translocation with chromosome 9 which results in a fusion gene known as BCR-Abl
associated with Chronic myelogenous leukemia
BCR-Abl
contains a portion that codes for a tyrosine kinase
in the nutated form of the protein the tyrosine kinase is constitutively (or always) on
tx options include: Gleevec (imantinib) which is a tyrosine kinase inhibitor
