IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Xenopatients 2.0: reprogramming the epigenetic landscapes of patient-derived cancer genomes.
Autor/es:
MENENDEZ JA; ALARCON T; COROMINAS-FAJA B; CUYÁS E; LOPEZ-BONET E; GARCÍA-MARTÍN A; VELLON L
Revista:
CELL CYCLE
Editorial:
LANDES BIOSCIENCE
Referencias:
Lugar: Austin, Texas; Año: 2014 vol. 13 p. 358 - 370
ISSN:
1538-4101
Resumen:
In the science-fiction thriller film Minority Report, a specialized
police department called "PreCrime" apprehends criminals identified in
advance based on foreknowledge provided by 3 genetically altered humans
called "PreCogs". We propose that Yamanaka stem cell technology can be
similarly used to (epi)genetically reprogram tumor cells obtained
directly from cancer patients and create self-evolving personalized
translational platforms to foresee the evolutionary trajectory of
individual tumors. This strategy yields a large stem cell population and
captures the cancer genome of an affected individual, i.e., the
PreCog-induced pluripotent stem (iPS) cancer cells, which are
immediately available for experimental manipulation, including
pharmacological screening for personalized "stemotoxic" cancer drugs.
The PreCog-iPS cancer cells will re-differentiate upon orthotopic
injection into the corresponding target tissues of immunodeficient mice
(i.e., the PreCrime-iPS mouse avatars), and this in vivo model will run
through specific cancer stages to directly explore their biological
properties for drug screening, diagnosis, and personalized treatment in
individual patients. The PreCog/PreCrime-iPS approach can perform sets
of comparisons to directly observe changes in the cancer-iPS cell line
vs. a normal iPS cell line derived from the same human genetic
background. Genome editing of PreCog-iPS cells could create
translational platforms to directly investigate the link between genomic
expression changes and cellular malignization that is largely free from
genetic and epigenetic noise and provide proof-of-principle evidence
for cutting-edge "chromosome therapies" aimed against cancer aneuploidy.
We might infer the epigenetic marks that correct the tumorigenic nature
of the reprogrammed cancer cell population and normalize the malignant
phenotype in vivo. Genetically engineered models of conditionally
reprogrammable mice to transiently express the Yamanaka stemness factors
following the activation of phenotypic copies of specific cancer
diseases might crucially evaluate a "reprogramming cure" for cancer. A
new era of xenopatients 2.0 generated via nuclear reprogramming of the
epigenetic landscapes of patient-derived cancer genomes might
revolutionize the current personalized translational platforms in cancer
research.