Cancer Treatment: A Rational Approach Flashcards
why has the incidence of breast cancer increased?
b/c of increased screening
explain functional genomics and breast cancer
looks at the expression array of several genes dictating a good/poor signature
good: underexpression of proliferation genes & overexpression of immune response
which patients do NOT benefit from additional chemotherapy?
patieints w/ a ‘good signature’
what is the functional constriction in the development of chemotherapeutics?
only a small subset of defective proteins are suitable targets for cancers drugs
what in cancer patients determines if they’re good targets for drug intervention?
biochemical subtleties
Gleevec is a
tyrosine kinase inhibitor
Gleevec reduces the activity of what fusion protein?
Bcr-Abl
Bcr-Abl is a fusion protein that is active in what type of cancer?
chronic myelogenous leukemia (CML)
Gleevec converts
leukemic cells back to normal granulocytes
with Gleevec treatment qPCR analysis confirmed the dramatic reduction of
expression of Bcr-Abl fusion gene
patients w/ PML can be treated w/
PML: promyelocytic leukemia
all-trans retinoic acid
what types of responses can be produced w/ the use of cancer drugs?
- kill cancer via apoptosis
- induce differentiation
many chemotherapeutics damage chromosomes causing
mitotic catastrophe
sends cell into apoptosis
chemotherapeutics have a
therapeutic window
what is a therapeutic window?
where the efficacy is the highest and the toxicity is the lowest
natural compounds can be
- effective
- less toxic
EGCG in green tea binds to the
anti-apoptotic Bcl-XL protein
what is the method that was discussed with selective targeting of cancer cells?
- adding staurosporine
- adding camptothecin
- removing both drugs
staurosporine arrests the cell
at G1 restriction point preventing S phase
camptothecin causes
DNA damage during S-phase causing apoptosis
cancer cells DO NOT arrest in
G1
list 3 strategies targeted against cancer that focus on infection and inflammation
- antibiotics: gastric cancer
- NSAIDS: IKK inhibitors
- vaccines: cervical/liver cancer
list some oncogenes that show premanent regression
- H-ras
- K-ras
- Bcr-Abl
- myc
list some oncogenes that show presistence or relapse
- myc
- wnt
- neu
human tumors produce high levels of
CD47
what is the function of CD47?
to block the immune system from targeting and destroying cancer cells
in mice, treatments w/ doses of anti-CD47 caused
tumors to shrink & disappear
explain the treatment of ultrasound + radiation
microbubbles pass through the circulatory system and burst with pulses of ultrasound to destroy blood vessels
the treatment of ultrasound and radiation is currently being tested to break down the
blood-brain barrier
what reactivates the p53 protein?
thiosemicarbazones
what are the effects of thiosemicarbazones?
- tumor shrinkage
- slowed growth
- does NOT affect non-cancer cells
what is a unique cancer drug delivery system?
nanolipogels (NLGs)
NLGs accumulate in the
leaky blood vessels of tumors
what are the 2 components of NLGs?
- TGF-B inhibitor
- IL-2 protein
IL-2: recurits immune response
what was the effect of NLGs in mice?
- delayed tumor growth
- sent tumors into remission
- increased survival rates
Golden Retrievers and Humans have what type of bone cancer in common?
osteosarcoma
why were blind mole rats not able to grow cancer?
- no tumor growth
they live in low oxygen environments and this prevented the angiogenesis
