3-cancer molecular therapy Flashcards
treatment modalities
- chemotherapy
- radiation
- surgery
conventional chemotherapy exploits _______ to target tumor cells
growth differences
conventional chemotherapy can be ___ and ____
cell cycle specific
non cell cycle specific
what is the most prominent target for differential toxicity to tumor cells
DNA synthesis
G1 progression occurs in response to growth factor
originated MAPK signaling at the restriction point
S progression is essentially totally committed to
DNA synthesis
principle of cell cycle phase specific agents
-usually attacks S phase of the cell cycle
-depends on knowledge of tumor kinetics
-exploits distributed doses
what does Ara- C target
DNA replication
what does methotrexate target
DHFR
what does hydroxyurea target
ribonucleotide reductase
how does methotrexate work?
MTX is a folic acid analogue that targets DHFR which synthesizes DNA precursors and allows DNA synthesis
methotrexate is _____ specific
S phase
hydroxyurea is _____ specific
S phase
how does AraC work?
AraC adds a fraudulent nucleotide and targets DNA replication
principle of cell cycle non specific agents
-induce apoptosis without cell cycle specificity
-typically targets faster metabolism tumors
examples of cell cycle non specific agents
-anthracycline
-cis-platinum
what is anthracycline
binds DNA but causes widespread cellular damage
what is cis-platinum
cross links dna
what are hormone sensitive tumors and an example
some tumors depend on a hormone to grow
breast cancer- depends on estrogen
what are newer and experimental therapeutic modalities ?
-signaling and small molecules
-differentiation induction therapy
-siRNA, miRNA
-antibody therapy
-bone marrow transplantation
-gene array analysis to monitor response
small signaling molecule principle
growth factor signaling restricts cell cycle
principle of differentiation induction
convert the tumor to a near normal cell, relieving tumor burden and restore differentiated cell function
principle of antibody drug therapy
-use a monoclonal antibody to target a tumor specific antigen
-use a monoclonal antibody to target a molecule on which tumor growth depends on
principle of bone marrow transplantation
-treat patient with cytotoxic agents to aggressively kill tumor and hematopoietic capability is destroyed
-restore hematopoietic capability by bone marrow engraftment
gene expression arrays
means of monitoring tumor and host response to the drug to optimize drug delivery, minimize toxicity
2 small RNA mediated ways to regulate expression of a targeted gene
anti-sense
siRNA
ribo-switch
antisense
a fragment from a coding region that binds the mRNA and targets the dsRNA for degradation via ribonuclease H
siRNA
fragment transcribed from non-coding RNA that specifically targets complementary mRNA and recruits the RISC complex to degrade the mRNA
-results from pol3 produced miRNA digested by DICER and typically targets 3’ UTR
ribo switch
larger fragment derived from non coding mRNA that binds the mRNA, recruits other proteins and gets translated
what are synthetic RNAs that mimic/target microRNA
miR
what is miR
small fragments of non coding RNA that have cell type specific expression
-targets a number of putative regulatory genes for mRNA degradation by binding at 3’UTR
miRNA controls cell
proliferation and differentiation
miR is differentiated by size
small, intermediate, long
advantage of drugs mRNA expression is their _________
potential target specificity
what are the major cyclins that govern G1, S, M
D, E, A, B
cyclin/CDKs are regulated by
CDKIs, p21, p27
goal of combination therapies
mitigate toxicities and maximize targeted toxicity
redundant function contributes to
survival
