Wk 3 Cancer Flashcards
(30 cards)
What is a driver mutation?
A mutation that promotes development or progression of cancers
What is a passenger mutation?
A mutation without phenotypic consequence for the cancer cell
What are subclones?
clone selected from a clone especially after a mutation occurs
What are 5 hallmarks of cancer?
- senescent cells
- polymorphic microbiomes
- nonmutational epigenetic reprogramming
- unlocking phenotypic plasticity
- FINISH
What is an analogy for tumors?
Like wounds that do not heal (chronic inflammation)
Targets to limit cancer cell growth
- DNA synthesis
- purine ring biosynthesis
- block topoisomerase
- block signaling pathways
- inhibit ribonucleotide reductase
Targets to limit cancer cell growth
- DNA synthesis
- purine ring biosynthesis
- block topoisomerase
- block signaling pathways
- inhibit ribonucleotide reductase
What is induction chemotherapy?
treatment of disease to achieve remission
What is consolidation chemotherapy?
given after induction to control microscopic disease
What is maintenance chemotherapy?
given over long-term basis to maintain remission
What is salvage chemotherapy?
chemotherapy given after relapse or refractory to previous therapy
What does hydroxyurea do?
Inhibits ribonucleotide reducase, inhibiting nucleotide synthesis
What are the pyrimidines?
Cytosine, uracil, thymine
What are the purines?
adenine, guanine
What is a nucleoside?
What is a transversion?
mutation to different type (pyrimidine to purine or visa versa)
What is a transition?
Mutation from one purine to another (or pyrimidine)
What is PRPP?
phosphoribosyl-1-pyrophosphate
- its conversion to 5-PR-1amine is the committed step in purine synthesis and is highly regulated
- either talking about do novo purine synthesis OR cancer drugs?
Why is glutamine so imp?
Imp role in purine and pyrimide synthesis
-cancer cells love it b/c they use it to make nucleotides
-imp in de novo synthesis of nucleotides
3 sources of nucleotides in humans
- dietary uptake - minimal
- most cells can synthesize nucleotides do novo, but hepatocytes are responsible for most production w/ RBCs transporting products to other tissues
- most cells can salvage free bases by attaching them to PRPP to make nucleotides. * Base analogs as drugs that can be taken up by cells but have altered properties
-utilized the most as we try to stop cancer replication w/ uptake -> harm the cell
What is HGPRTase?
enzyme that salvages prodrugs, converting them to drug forms that can inhibit steps in purine snythesis or cause mutations after being incorporated into DNA
What does adenosine deaminase (ADA) do?
acts in RNA/DNA catabolism
-lack of ADA -> severe combined immunodeficieny (SCID) due to increased dAMP (which -> increased dATP), shutting down RNR (ribonucleotide reductase)
What does lack of HGPRTase cause?
Lesch-Nyhan syndrome
What does catabolism of RNA/DNA produce?
uric acid, since we lack uricase
-excess uric acid precipitates -> gout and tumor lysis syndrome (kidneys)
