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Frank Bures: How to judge the age of a cancer

December 16, 2018
Dr. Frank Bures

“How old is your cancer?” is the title of a one-page commentary from the Jan. 11, 2011, Scientific American. I discovered it when plowing through piles of meticulously preserved precious medical periodicals and grudgingly “thinning” them. It was a brief report on a paper from the journal Nature on experimental screening techniques specifically to detect pancreatic cancer.

The problem is that, at the time of initial diagnosis of pancreatic cancer, the typical patient tragically has only five years to live. An early diagnosis is actually a too late diagnosis. A research group from Johns Hopkins University suggested that cancer causing mutations arise in normal cells 10 years before they transform into actual cancer cells, and another five years pass prior to those cell types spreading to become deadly.

This group did gene sequencing of the cancer cells from seven patients who died of late stage pancreatic cancer. Individual tumor cells of the same cancer line contained mutations different from each other. Using mathematical models of cell replication, they constructed a “family mutational tree” to estimate the 10 and 15 years development.

A research group from the University of California-Los Angeles compared RNA sequences found in the saliva of 60 still treatable pancreatic cancer patients with that of 30 cancer-free folks. They identified four different RNAs that, when taken together, correctly diagnosed the pancreatic cancer 90 percent of the time.

The article also cited optical (microscopic) technology, which recognized various stages of the pancreatic cancer cells 95 percent of the time. In 2011 any of these approaches were not available commercially. In trying to search, and search again (research?), for these today under tests for pancreatic cancer, they are not listed. The only ones utilized are machines to make images of your pancreas or peer into your bowel with a scope, as ultrasound or magnetic resonance imaging/MRI, or endoscopy. No reliable blood or other body fluid tests are done.

The question of how long you have had a cancer is very complicated because even in one kind of cancer cell type, individual tumors grow and act differently. A current vogue is to hold up prostate cancer as an example of a slow growing kind, even discouraging treatments because you, the old geezer, could die from something else before the prostate enemy takes you down. That’s a hard sell to someone dying from prostate cancer, or the surviving family.

Ovarian cancers are another bad actor because their presence is sinisterly subtle. With the push to “save” monetary resources (which saves insurance companies from paying out in order to keep it for executive salaries) even the blood tests for it and psa’s for prostate are discouraged beyond a certain age.

The problem biologically is that any individual tumor will retain tendencies to grow more like its original tissue type for quite a while until the genes regulating and suppressing cell multiplication are mostly lost, and the cells only know how to divide, multiply, and destroy adjacent or distant normal tissues. New and different gene mutations arise during the cancer’s development until it reaches its ultimate aggressive behavior.

Treatments are now being tailored to fit gene mutational patterns or panels analyzed in a person’s cancer. This is common with many breast cancer types. To guess how old a cancer might be from those gene patterns is tried, but doesn’t change what is going to be used for treatment. You have work with what is happening now, not in the past.

Skin cancer may have a slight advantage in deciding how long it has been brewing, if the spot in question has been visible and noticed in the past, and the patient has observed changes in it. The three main kinds of skin cancer are basal cell, squamous cell, and melanoma. It’s redundant to say “malignant melanoma” because all of them are. I have definitely found basal cells in growths the owner tells me have been there anywhere from two to 20 years, quietly residing on their hide. When I would examine the spot, I would see it was unquestionably cancer and growing. So what happened to make it go bad? That’s as unanswerable as how big will it get, etc.

Our tools to find “early” cancers are primitive and woefully inadequate. We still make a diagnosis by staring through a microscope at a dead hunk of flesh, and prognosticate. We lack methods to measure real dynamic biological activity on a subcellular level to learn any tumor’s growth tendencies.

Of course, an easy comparison is trying to guess and measure predictably the maturity rate any teenager is achieving at any given point. A plaque I used to have on my office wall said, “Raising a teenager is like nailing Jell-o to a tree”. Sort of the same might be said of measuring the age and rate of malignant transformation of a cancer.

It’s redundant to say “malignant melanoma” because all of them are.

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