Recent results obtained from research on the intermediary metabolism of
tumor cells have uncovered the biochemical reprogramming that takes place upon
malignant transformation. Many features have been highlighted that are currently being
exploited for specific chemotherapy. Many more will become available shortly as a
consequence of the recognition of potentially useful targets for treatment. General
interest in this area can be gauged by the number of recent patents that have been
deposited, or are in the process of application. Because the metabolic subversion that is
a hallmark of cancer cells involves disruption of its homeostasis, the regulatory
pathways dealt with in this chapter were broadly divided into those that encompass the
main stages of the cell cycle and its various regulatory mechanisms and those that
involve the aerobic glycolysis typical of cancer cells. It becomes apparent that both, the
cell cycle and the intermediary metabolism are interconnected and rely on reactions
many of which are dependent on kinases and phosphatases. Kinases and phosphatases
are responsive to cellular redox signaling and may have a key role in determining
whether cells progress towards malignant transformation as a result of continuous
oxidative stress. The data discussed here underline aspects of the signaling pathways
that lend themselves to specific inhibition by natural and synthetic compounds. The
mitochondria and its role in programmed cell death is briefly commented, but special
emphasis is placed on biochemical regulation at the level of chromatin structure,
particularly the reactions that involve acetylation and deacetylation of histones. Within
this context, inhibitors that act on histone deacetylases are discussed as promising
alternatives to available treatments.
Keywords: Acetylation, aminopeptidases, angiogenesis, ATP, CDKs, chromossomes,
CKIs, homeostasis, hypoxia, kinases, lactate, metabolomics, mitochondria, oncogenes,
phosphatases, pyruvate kinase, ROS, sumoylation, ubiquitin.