Stay Trippy: Cancer’s Rollercoaster

 

Juicy J loves to stay trippy, and so does cancer. Cancer is really weird; what it does to a body in its entirety is rooted in what happens at the molecular level. People have had ideas to explain the behavior of this disease, some which have been dismissed as wacky, while other ideas have stood the test of time.

Interestingly, the Warburg hypothesis, developed by Otto Warburg, has undergone a rollercoaster effect.

Warburg observed something very unique about cancer cells in that they do not fully break down glucose (sugar) to generate the full potential of ATP molecules. In fact, cancer cells are extremely “inefficient” at breaking down sugar and produce lactic acid as a byproduct. Yeah, that thing your muscles produce when they are deprived of oxygen! What’s interesting is that cancer cells produce this even when oxygen is rich. Since a fully functioning mitochondria, or “powerhouse of the cell” is imperative to full breakdown of glucose, Warburg postulated that the lack of full glucose breakdown, or the accumulation of lactic acid, was a result of a mitochondria gone bad in cancer. That’s it! He solved the riddle! Mitochondrial dysfunction was the cause of cancer!

Well, unfortunately that was not the case (at that time), and what he observed was not a cause of cancer, but more a passenger effect of the disease. What science later discovered was that a main driver of cancer was the activation of genes that promote uncontrollable growth, or here’s a riddle, the deactivation of negative regulator of growth (a double negative). So, for years after Warburg’s theory, the scientific community, alongside advances in genetics became obsessed with finding that magical gene/protein that we could target chemically and save the world once and for all.

Turns out it’s not that simple either. What’s a hit for one cancer type may be irrelevant to another, and even these genes/proteins that we identify as a hit, need to be working alongside another wacky component of the cell to actually get a cancer rolling. A perfect storm…for the Warburg hypothesis. Interestingly, the scientific community didn’t really give a shit about Warburg’s theory until about 15 years ago when all of a sudden, the role of the mitochondria in cancer began to resurface. Now there are drug companies aiming to target that magical mitochondrial protein in cancer. I even attended a conference in Snowbird, Utah recently (go there if you love to ski btw), that was entitled “tumor metabolism.” It attracted many of the world’s rock star scientists (I was just a peasant in the crowd), but we all came together as a scientific community, and the recurring theme was…targeting the mitochondria in cancer. How happy Otto Warburg would be.

Michael Dahabieh, Ph.D. candidate

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Angie Olivo