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2017 ; 8
(24
): 38642-38649
Nephropedia Template TP
gab.com Text
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English Wikipedia
A mathematical theory of the transcription repression (TR) therapy of cancer -
whether and how it may work
#MMPMID28454100
Chen Y
; Wen H
; Wu CI
Oncotarget
2017[Jun]; 8
(24
): 38642-38649
PMID28454100
show ga
Transcription repression (TR) therapy of cancer has been widely discussed. Here,
TR refers to global repression of transcription rather than specific targeting of
cancer-causing genes such as MYC. TR drugs inhibit transcription by binding to
the transcribed DNA or to RNA polymerase; for example, actinomycin D has been
extensively used in research and therapy to shut down transcription globally
[1-7]. As proliferating cells demand a high rate of transcription, restricting
transcript production could be effective in slowing down cell proliferation.
However, TR also deprives other less proliferative cells of new transcripts, thus
leading to substantial toxicity [1, 8, 9]. We now develop a mathematical theory
to exploit the greater demand for transcription in highly proliferating cells. A
new strategy, referred to as the TRR (transcript repression-recovery) model,
would insert a recovery phase to allow the more slowly proliferating cells to
recover. It is most effective to have strong blocking for a short period (a few
hours) followed by a longer recovery phase in each cell cycle. Hence, TRR can
potentially achieve selective killing of cells based on their global
transcription needs but precise fine-tuning is necessary.