This is clearly a mechanism that could be potentially targeted in cancer therapy, for example by blocking glucose transporters. But more generally it speaks to the growing importance of metabolism in cancer treatment. It seems to me that since the 1970s or so, partly because of discoveries regarding oncogenes like Ras and Src and partly because of the explosive growth in sequencing and genomics, genetics has become front and center in cancer research. This is a great thing but it's not without its pitfalls. In the race to decode the genetic basis of cancer, one gets the feeling that the study of cancer metabolism has fallen a bit by the wayside and is now being resurrected. In some sense this almost harkens back to an older period when cancer was conjectured to be caused by environmental factors affecting metabolism.
It's gratifying therefore that things like the Warburg Effect are being recognized. As the article points out, one of the simple reasons is because while many (frighteningly many in fact) genes might be mutated in cancer, a cancer cell usually has only a few ways to get energy from its surroundings: the range of targets is thus potentially fewer when it comes to energy. The recognition of this effect also speaks to the commonsense view that we should have a multipronged approach toward cancer therapy: genetics, metabolism and everything in between. Judah Folkman's idea of starving off a cancer cells's blood supply is another approach, what we may call a 'mechanical' approach (all of cancer surgery is a mechanical approach, in fact).
I could not help but also note the interesting coincidence that this tussle between emphasizing genetics vs metabolism has played out in another area which seems quite far removed from cancer medicine: the origin of life. For the longest time people focused on how DNA and RNA could have been formed on the primordial earth. It's only about 20 years ago or so that "metabolism first" started getting emphasized too: this approach emphasized the all important role that the evolution of life's energy generating apparatus (in the form of proton gradients and ATP) played in getting life jumpstarted. The metabolism first viewpoint really took off with the discovery of deep sea hydrothermal vents which can generate primitive energy-creating biochemical cycles based on proton gradients, alkaline environments and diffusion through tiny pores in the vents. Biochemists like Nick Lane and Mike Russell have been pioneers in this area.
The renewed focus on metabolism in treating cancer as well as in exploring the most primeval characteristics of life seems to me to bring the study of life in both health and disease full circle. Just like you cannot discuss the genetics of life's origins without discussing life's source of energy, so can you also not disrupt cancer's spread by disabling its genes without disabling its source of energy. Both are important, and emphasizing one over the other seems mainly to be a function of research fads and fashions rather than objective scientific reasoning.
As an amusing aside, the father of a very close friend of mine knew Otto Warburg quite well when he worked in Vienna in the 50s. Here's what he had to say about Warburg's scrupulous lab protocols: "One story I've always remembered was that he would clean his own glassware, used in experiments. He didn't trust any low-level dishwasher or junior staff around the lab. He wanted to make sure everything was perfect. I can confirm that even a tiny 'foreign fragment' in glassware can wreck an experiment."
The NYT article was wonderful! It was published alongside another great article by Dr. Mukherjee. Recent work in the Goga Lab at UCSF has already demonstrated early success in inhibiting growth by targeting an aberrant metabolic pathway in triple-negative breast cancer cells. I'm very excited to see how metabolism and genetics will be combined to improve our understanding of cancer and to eventually design better treatments for patients.
ReplyDeleteAlso, the combination of immunotherapy and metabolic engineering has some promise (see doi:10.1016/j.immuni.2016.01.021). Worth noting that a lot of the renewed interest is a tool driven revolution due to NMR/MRI and LC/GC-Mass Spectrometry.
ReplyDeleteThe NYT also published an article on the link between cancer and evolution in terms of which factors played the most decisive roles. They concluded, "For cancers like those of the bone and brain, chance seemed to rule. But at the other end of the spectrum were those that were more ;deterministic'— like lung cancer and basal cell carcinoma, a usually harmless skin malignancy where sunlight plays a deciding part. Also at that extreme were rare cancers mostly determined by inherited defects, like some familial forms of colon cancer."
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