17 - Drug and Immune Resistance Flashcards
What are pre-malignant cells called?
dysplastic
What are the 4 major types of treatment for cancer?
immunotherapy | chemotherapy | surgery | radiation
What are MDR protein channels?
multiple drug resistance protein channels = pumps drugs and toxins out of cell
What are ABC transporters?
ATP Binding Cassette transporters = MDR protein channels/pumps
What are the 4 ABC proteins that are involved in MDR?
p-glycoprotein | multidrug-resistance-related protein (MRP) | lung resistance-related protein | breast cancer resistance-related protein
What gene produced p-glycoprotein?
MDR gene
How many transmembrane domains do ABC transporters have?
17 = huge
What is p-glycoprotein?
ATP-dependent drug efflux pump
Where do p-glycoproteins pump drugs from?
cytosol and within plasma membrane
What is “cross-drug resistance” of some pumps?
one pump resistant to different kinds of drugs
Is it better to have 3 drugs that do the same thing so it hits stronger OR 3 drugs each having a different mechanism hitting the cells in different ways?
different mechanisms
What is the issue of having variants of MDR?
all may need different inhibitors since all are different/variants
What are 4 solutions for overcoming MDR?
use chemosensitizing agents to inhibit the pump | saturate with high concentration of the drug | new drugs not subjected to known resistance mechanisms | drug combos not subject to same resistance mechanisms
What are chemosensitizing agents (modulators)?
non-toxic compounds to make MDR cells more susceptible to the toxicity of drugs
How does bioavailability affect drug efficacy and toxicity?
need a high drug bioavailability to be effective and toxic to tumor cell
How can modulators be too toxic?
can block all of the pumps of other cells such as liver and kidney = need for detoxification
Since cytochrome p450 metabolizes drugs, how can you overcome this to increase the efficacy of your anti-cancer drug?
lock and key = make a drug that will fit the cytochrome p450 enzyme = inhibit it
What are 2 types of enzyme inhibitors?
competitive inhibitor = on active site | non-comepetitive inhibitor = changes shape of active site
What is pharmacokinetics?
time course of ADME processes
What does ADME stand for?
absorption | distribution | metabolism | excretion
In ADME, what is the absorption process?
passage of drug from administration site to circulation
In ADME, what is the distribution process?
protein binding followed by target specific and non-specific tissue uptake
In ADME, what is the metabolism process?
Phase I and Phase II of metabolizing the drug | changes in each person = why clinical trials take long
In ADME, what is the excretion process?
removal of intact drug
