“I really try to put myself in uncomfortable situations. Complacency is my enemy.” - Trent Reznor. Nine Inch Nails
My time in the tent this past week wasn’t spent sliding down spirit caves with power animals or searching for blue orchids, I worked. Or to put a more fine point on it, I studied in solitary quietude.
One of my lifelong friends, now gone, was a philosophy professor and he always said, ‘Luke (That’s how I was known back then before becoming Yer Big Dog I mean). Life isn’t about answers, it’s about the questions you ask.’
And now that I’m 3 for 3 for dogs with cancer, I have a lot of goddamn questions. We all do.
But being back in the tent again I couldn’t help but wonder if I had missed something the first time. And the second time. So I need to start again. With the first question.
What is cancer?
According to Withrow & MacEwen’s ‘Small Animal Clinical Oncology‘, there are two generations or iterations of our understanding of cancer. The first, Gen 1 let’s call it, was from a 30 year compilation of research published in 2000 by Drs. Hanahan and Weinberg called the ‘Six Hallmarks of Cancer’.
They were attempting to distill the down and outright differentiation, the lowest common denominator, the absolute zero, between a normal cell and a cancer cell and they accomplished something close to it – an approximation that became an early and important precedent.
Before I begin with my folksy analysis of it, I encourage you to purchase this inestimable tome. Most nearly all of the thought leaders and minds both past and future in comparative oncology contributed to it and I’m humbled even at an attempt to understand it.
Heck the flow charts look like a John Madden schematic to me. But here we go.
The Six Hallmarks of Cancer
1. Self Sufficiency of Growth Signals.
This is the ‘To Be or Not to Be’, the Hamlet, shall we say, of the hallmarks. Cancer is a genetic disease but not all predisposed or mutated cells become malignant. Proto-oncogenesis doesn’t presuppose oncogenesis.
But once it ‘Be’, like Hamlet’s ill-fated love for Ophelia, a cascade of events occur very few of which can stop the inevitable.
2. Insensitivity to Antigrowth Signals.
If only cancer was a cell on a homicidal steroidal rampage, unchecked and running amok, like Arnold Swarz… shit, the Terminator, well, we’d deal with it kind of the same way. We gave him the run of 80′s action films, made him the Governator but, whoa, president and potentially the ruler of the universe?
That’s what Tumor Suppressor Genes, or the Kindergarten Cops, do and this is important.
Back in the 1970s, before Arnold was clad in a loin cloth in Conan, scientists were trying to understand retinoblastoma* and in researching its heritable traits they discovered the existence of a tumor suppressing gene which in subsequent research yielded the discovery of p53 (more on p53 later).
But the ‘Terminator’ will always be back. Like what Michael Chrichton wrote in Jurassic Park. ’Nature finds a way’. So does cancer and it found a way to suppress and/or inactivate the biochemical mechanisms and fool-proof machinery incorporated into your DNA to prevent tumor suppressor genes and p53.
This is the point at which pink elephants come into the equation.
My friend, Pete, loved pink toys. It made him happy. In nature, happy, is referred to as homeostasis. It’s the balance, the bad v good ballad that’s part of the Dance of life.
If only cancer was an aberration, a beefy Austrian bad actor named Arnold that defied all odds. But it isn’t. And it only gets worse.
3. Evasion of Cell Death.
The Cell Cycle ain’t complicated in a cradle to grave sense. Cells procreate to sustain the life of tissue, organ systems, and ultimately self. Left unchecked, hell, it’d become part of the Kardashian franchise but pre-programmed in a cell’s genetic structure is a stop function called apoptosis.
However, to quote the textbook, ‘Cancer cells, through a variety of strategies, can acquire resistance to cell death and apoptosis.’ I call this the Br’er Rabbit Effect.
I’ll stop here and continue with 4-6 tomorrow. I’ll start again.
2 Dogs 2,000 Miles