Efforts to understand the mechanistic principles driving
cancer metabolism and proliferation have been lately governed by genomic, transcriptomic and proteomic studies. This paper analyzes the caveats of these approaches. As molecular biology's central dogma proposes a unidirectional flux of information from genes to
mRNA to
proteins, it has frequently been assumed that monitoring the changes in the gene sequences and in
mRNA and
protein contents is sufficient to explain complex cellular processes. Such a stance commonly disregards that post-translational modifications can alter the
protein function/activity and also that regulatory mechanisms enter into action, to coordinate the
protein activities of pathways/cellular processes, in order to keep the cellular homeostasis. Hence, the actual
protein activities (as
enzymes/transporters/receptors) and their regulatory mechanisms ultimately dictate the final outcomes of a pathway/cellular process. In this regard, it is here documented that the
mRNA levels of many metabolic
enzymes and transcriptional factors have no correlation with the respective
protein contents and activities. The validity of current clinical
mRNA-based tests and proposed metabolite
biomarkers for
cancer detection/prognosis is also discussed. Therefore, it is proposed that, to achieve a thorough understanding of the modifications undergone by proliferating
cancer cells, it is mandatory to experimentally analyze the cellular processes at the functional level. This could be achieved (a) locally, by examining the actual
protein activities in the cell and their kinetic properties (or at least kinetically characterize the most controlling steps of the pathway/cellular process); (b) systemically, by analyzing the main fluxes of the pathway/cellular process, and how they are modulated by metabolites, all which should contribute to comprehending the regulatory mechanisms that have been altered in
cancer cells. By adopting a more holistic approach it may become possible to improve the design of therapeutic strategies that would target
cancer cells more specifically.