Antagonists of novel calcium channels as promising targets
for inducing apoptosis in hormone-dependent and
independent prostate cancer and for delaying
androgen-independence: Strategic analysis and target
exploitation
Apoptosis remains a primary target for the treatment of
prostate cancer. Despite considerable efforts few
apoptotic candidates have progressed through to advanced
stages of development. One particularly exciting target
for apoptosis is the calcium signaling pathway, in
particular store-operated calcium channels (SOCs) which
are responsible for maintaining calcium levels in
intracellular organelles. Blockade of SOCs induces
apoptosis. Restricted prostatic expression of the novel
SOCs-related protein CaT1 has been demonstrated and linked
to tumor progression. Strong evidence exist to suggest
that inhibitors of CaT1 may:
1. induce apoptosis in a wide range of prostate cancer
phenotypes;
2. reduce the development of androgen-independence; and
3. have activity in androgen-resistant cells.
Development of this target may produce highly effective
treatments with limited side-effects. This dossier:
> Overviews the concept of targeting calcium
channels in the treatment of cancer and highlights novel
calcium channels that have recently been identified
> Analyzes calcium channel blockers in development
for the treatment of cancer
> Suggests screening architectures to develop
therapeutic candidates
> Offers practical input to help expedite the
screening process focussing on novel HTS/MTS assays
designed to reduce bench to clinic down-time and assays
using human material to fully characterize the clinical
potential of hits
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