Mara Stewart (now Gladstone) is
a Post-doctoral fellow. Here is the abstract of her latest paper (PubMed Link).
Dis Model Mech. 2011 May 2. [Epub ahead of print]
Combinatorial
effect of maytansinol and radiation in Drosophila and human cancer cells.
Edwards A*, Gladstone M*,
Yoon P,
Raben D,
Frederick B,
Su TT.
Molecular,
Cellular and Developmental Biology, University of Colorado, Boulder, CO
80309-0347, USA.
*shared
first-authorship
Abstract
Combination therapy, in which
two or more agents are applied, is more effective than single therapies for
combating cancer. For this reason, combinations of chemotherapy with radiation
are being explored in clinical trials, albeit with an empirical approach. We
developed a screen to identify, from the onset, molecules that act in vivo in
conjunction with radiation, using Drosophila as a model. Screens through two
small molecule libraries from the NCI Developmental Therapeutics Program
yielded microtubule poisons; this class of agents is known to enhance the
effect of radiation in mammalian cancer models. Here we report an analysis of
one microtubule depolymerizing agent, maytansinol isobutyrate (NSC292222;
maytansinol), in Drosophila and in human cancer cells. We find that the effect
of maytansinol is p53 dependent in Drosophila cells and human cancer cells,
that maytansinol enhances the effect of radiation in both systems, and that the
combinatorial effect of drug and radiation is additive. We also uncover a
differential sensitivity to maytansinol between Drosophila cells and Drosophila
larvae, which illustrates the value of studying cell behavior in the context of
a whole organism. On the basis of these results, we propose that Drosophila
might be a useful model for unbiased screens through new molecule libraries to
find cancer drugs for combination therapy.
See also:
Mara Stewart & Tin Tin Su. A screen for radiation
sensitizers of Drosophila checkpoint mutants. In ÒCell Cycle Checkpoints:
Methods and ProtocolsÓ. Edited by Willis Li. Humana Press, in press
for 2011.
Drosophila radiation biology that forms the basis for
the screen is in Jaklevic et al. 2006 (PDF).
Mara is assisted in her screens by excellent undergrads.
e-mail Mara (mara.stewart@colorado.edu)