Regulatory nuclear pathways feeding into the transcription of cancer-relevant
molecules have emerged as the next frontier in pathway-centered cancer therapeutics.
The signifi cance of nuclear signaling in cancer is also evident by the convergence of
a large number of signal transduction pathways continuously sensing extracellular
milieu. The cumulative outcome of deregulated cytoplasmic and nuclear signaling
is to provide a favorable environment for a cancer cell to survive by overriding death
signals, to sustain an excessive hyper-mitogenic activity, to feed into deregulated
cell cycle progression, and to support a defective segregation of genetic material
during mitosis leading to genomic instability, to name a few essential hallmarks of
cancer progression. Among other processes, chromatin remodeling and epigenetic
modifi cations are two important nuclear regulatory arms of transcription that have
offered a battery of exciting therapeutic opportunities in terms of specifi city by
focusing on specifi c modifi cation or modifi cations of histone or nonhistone pro-
teins, domain-targeting, enzymatic activities such as histone deacetylases, histone
acetyltransferases, histone demethylases, or splicing factors – as all of these activi-
ties are widely deregulated in multiple human cancers. A large body of work during
the last decade has demonstrated that these are targetable areas of translational can-
cer medicine, and therefore, a large number of small molecules or agents targeting
these biological processes are rapidly moving through the preclinical development
pipeline to clinical studies.
Nuclear Signaling Pathways and Targeting Transcription in Cancer by Rakesh Kumar