Exam 4 Flashcards
What are the three classes of tumors
Indolent tumors
Aggressive tumors
Intermediate tumors
Describe indolent tumors
Squamous cell and skin
Low invasive potential
See if it’s even worth treating
Describe aggressive tumors
More likely to metastasize
Use surgery, drugs, immunotherapy
Describe intermediate tumors
May or may not metastasize
Can use extraction but may not be enough
Which class of tumor is trickier to determine how to treat
Intermediate
what are the two classes of drugs
DNA modifying agents
antimetabolites
what are examples of DNA modifying agents
alkylating agents, cross-linkers, strand breaks
what are examples of antimetabolites
base analogs, topoisomerase inhibitors, microtubule inhibitors
what are the four ways drugs act on cancer cells
make cancer cells differentiate
activate apoptosis
deprive cells of anti-apoptosis signals
cause mitotic catastrophe
what is an example of making cells differentiate
in APL leukemia, get blast cells to differentiate into PMN neutrophil cells
what is an example of depriving cells of anti-apoptosis signals
inhibit activation of Akt/PKB
what are the ways to pick a target
can we mimic tumor suppressor function
enhance caretaker of DNA repair mechanisms
oncoproteins
is the target druggable
protein to protein interactions
how many kinases do we have
518
most kinases are what type
STKs
what drug targets kinases and how does it work
Tarceva takes spot in EGF receptor kinase domain
describe the development of drugs
must bind and inhibit function at low concentrations—move on to tests in cell culture—tests in lab animals—phase I—phase II— phase III
what does drug testing in animals determine
pharmacokinetics and pharmacodynamics
what are pharmacokinetics
how effective it is in an organism
efficacy in vivo
does it accumulate in plasma or tissue
what are pharmacodynamic
ability to inhibit target in a treated tumor
what occurs in a phase I trial
measure drugs toxicity
use PK and PD values to determine the therapeutic window
what occurs in a phase II trial
measure effectivity
make decisions about what types of tumors to treat and at what stage
what occurs in phase III trials
look for a better response than from other available treatments
how many drugs make it through phase III
1%
Explain Gleevec and what type of cancer it works against
inhibits Bcr-Abl kinase activity and works against Kit and PDGF receptor
pancreatic cancer
What are examples of EGF receptor drugs
Tarceva and Iressa
How do Tarceva and Iressa work and what do they work against
inhibit kinase activity
effective in non small cell lung tumors
what is Velcade and what does it work against
proteasome inhibitor
NF-kB then can’t be degraded so apoptosis can occur
multiple myeloma
Explain Cyclopamine and what it fights against
false hellbore teratogen inhibits smoothened so Gli cannot promote proliferation
basal cell carcinoma
Exaplain Rapamycin and what it fights against
blocks mTOR activity and therefore Akt/PKB pathway
colon cancer
what are the plots called that we’ve been sing all semester
Kaplan-Meier plots
what are three ways macrophages fight cancer
present peptides to the immune system on MHC-2
detect stress signals on cells and destroy them
endocytose antigens bound to variable region of mutated cells
what are three ways macrophages help cancer
produce VEGF to promote angiogenesis
can degrade ECM and open up invasion past basement membrane
supply EGF to cells to promote proliferation
why do inactivating mutations lead to cancer in tumor suppressor genes but not proto-oncogenes
tumor suppressor genes are usually recessive so can still function with only one good copy
proto-onc are usually dominant so one mutation could ruin all of its functioning
what is a microarray
map of gene expression with various organs to help identify type of cancer and show over expression
