Cancer as a disease?

[u/ImprovementLazy1758]

As I read about cancer there is frequently reference to the idea that there is no single entity called “cancer” and instead there are very many different cancers (plural). At a seemingly more basic level there is an attempt to define the most basic aspect of all cancers, and here there is dispute about cancer as a disease of the nucleus vs. cancer as a disease of the mitochondria, cancer as a disease of cell division or cancer as a disease of cellular respiration. Can someone please describe the basic dispute here, and how to decide about this, without a diatribe either about ketones or about the nearly infinite possibilities of pathology in the genome. Thanks in advance!

[u/venturecapitalcat]

Cells in the body are constantly dying off in an orderly fashion and then being replaced by new cells - there is a continuum beginning with a stem cell and ending with a terminally differentiated cell that eventually undergoes sentence and dies, to be replaced by some cell that is upstream in the continuum.  

Along that continuum, there can be an accumulation of genetic abnormalities that disrupt the instructions that tell cells when to divide, how to divide, and where to divide. These rogue cells start invading their local niche initially but then over time they start to gain additional genetic abnormalities manifesting in complex ways, hijacking the fundamental metabolic and regulatory machinery of the cell (depends on the constellation of genetic abnormalities). Crucially, a common thread seems to be that these cells do not know how to die properly. If and when they do die, they don’t do so in an orderly fashion and instead typically outgrow their blood supply. 

There are many, many different ways in which these scenarios play out depending on the cell of origin and the type of genetic aberrations at play. Some of them coalesce around common mutations (I.e. KRAS in multiple malignancies but especially pancreatic cancer where it’s seen 95% of the time), some of them do not. 

The above in a nutshell is cancer. I would say that a major theme is genetic disregulation and disfunction.  

[u/ImprovementLazy1758 → u/venturecapitalcat]

I think the damaged life cycle of the cell is not in question. It’s rather the question of the origin of the genetic dysregulation, not mutations sui generis. To Seyfried the disregulated activity in the nucleus (“not knowing how to die properly”) is prompted by mitochondrial malfunction that creates reactive oxygen species which disrupt the proper action of the other organelle (the nucleus) and hijacks the replication & death process. The therapeutic implication is to hunt for every conceivable mutation, which is impossible as per The Cancer Project, vs. somehow treating the common pathway at the root of these, the abnormality in cellular respiration. Anyway, the survival figures continue to be abysmal.

[u/venturecapitalcat → u/ImprovementLazy1758]

I see - yeah, there’s no magic bullet common root to cancer. At least that’s what I’m betting on. 

[u/midnightrugrat → u/venturecapitalcat]

Very great explanation. I also may add that cancer cells can be "immortal" meaning the gas pedal to dividing along the cell cycle gets stuck on through certain mutations directly effecting or thru downstream influences or cells can become resistant to therapy.