Cancer-omics failure: warehouses, magic bullets, space/time and the Life of Brian in a cancer cell

Although the completion of the sequencing of the human genome led to massive efforts to catalog the differences between cancerous and non-cancerous cells at the level of expressed genes, so far this effort has not resulted in profound advancement in our understanding of cancer. Neither have there been major changes in therapeutic approaches based on knowledge at the molecular level, that is, the tendency is still to look for single, ‘magic-bullet’ genes/proteins as targets. It was natural enough to concentrate initially on the warehouse of genes and gene products. However, in retrospect, cataloging who or what enters/exits a warehouse does not seem to have been a very successful strategy for understanding the complexity of real life outside the warehouse. In fact, we might have anticipated that from the beginning: lots of different cells/organisms have essentially the same warehouse, but the result in terms of the living system can be totally different in space and time (Figure 1). At the other extreme, much conventional biology still concentrates on single proteins. Perhaps we should remember Jaron Lanier [101], one of the fathers of Virtual Reality, and follow his advice: invert our perspective, imagine that we are a single protein or individual (e.g., Monty Python’s Brian, whose mistaken identity turns into bitter-sweet satire [102]) and look around from where we are in a cancer cell. We are surrounded by an enormous crowd of apparently irrational individuals who buffet us in all kinds of ways. Some want to give us advertising flyers (e.g., small molecule substrates and regulators), some want to extract our watch or wallet (i.e., phosphatases and deacetylases), some would just as soon take an arm to get our watch (and proteases), some are streaming into the metro and simply sweep us along (i.e., cytoskeletal transport) and some are organized groups that want us to join their sect (i.e., protein complexes). Can all these encounters and activities have a purpose?