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2016 ; 7
(41
): 67626-67649
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On metabolic reprogramming and tumor biology: A comprehensive survey of
metabolism in breast cancer
#MMPMID27590516
Penkert J
; Ripperger T
; Schieck M
; Schlegelberger B
; Steinemann D
; Illig T
Oncotarget
2016[Oct]; 7
(41
): 67626-67649
PMID27590516
show ga
Altered metabolism in tumor cells has been a focus of cancer research for as long
as a century but has remained controversial and vague due to an inhomogeneous
overall picture. Accumulating genomic, metabolomic, and lastly panomic data as
well as bioenergetics studies of the past few years enable a more comprehensive,
systems-biologic approach promoting deeper insight into tumor biology and
challenging hitherto existing models of cancer bioenergetics. Presenting a
compendium on breast cancer-specific metabolome analyses performed thus far, we
review and compile currently known aspects of breast cancer biology into a
comprehensive network, elucidating previously dissonant issues of cancer
metabolism. As such, some of the aspects critically discussed in this review
include the dynamic interplay or metabolic coupling between cancer (stem) cells
and cancer-associated fibroblasts, the intratumoral and intertumoral
heterogeneity and plasticity of cancer cell metabolism, the existence of distinct
metabolic tumor compartments in need of separate yet simultaneous therapeutic
targeting, the reliance of cancer cells on oxidative metabolism and mitochondrial
power, and the role of pro-inflammatory, pro-tumorigenic stromal conditioning.
Comprising complex breast cancer signaling networks as well as combined
metabolomic and genomic data, we address metabolic consequences of mutations in
tumor suppressor genes and evaluate their contribution to breast cancer
predisposition in a germline setting, reasoning for distinct personalized
preventive and therapeutic measures. The review closes with a discussion on
central root mechanisms of tumor cell metabolism and rate-limiting steps thereof,
introducing essential strategies for therapeutic targeting.
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