The Evolution of a Cancer.

“If we can (fill in technological advance), why can’t we cure cancer?”

Implied in that question is an assumption that isn’t really true:  that cancer is a single thing, and some single treatment will affect it equally.  I think that most people have some understanding that the assumption is wrong, but how different (and how similar) are different types of cancer?

There is another aspect of cancer that isn’t focused on as closely as it should be:  any cancer, once started, behaves as an evolving population of (clustered) single-celled organisms.  This cannot be ignored when designing and carrying out treatment.


What is cancer?

In cancer, generally, damaged cells that should be doing something instead make more cells like them, and the damage tends to compound.  Some form masses that are self-limiting, some form continually-growing masses that affect the surrounding tissues, and some develop cells that migrate away and begin more tumors somewhere else.

What really makes cancers different is connected to two major factors:  1) what type of cell did the cancer start as?;  2)  what happened inside the first cell that turned it to cancer?

Not all of the cells in the body actually divide again once they are made and placed in a developing fetus.  A whole range of division-related genes are shut off, which makes it very difficult to turn such a cell cancerous. So some cell types (muscle would be an example) virtually never become cancer.  Cancers begin as cells that have division as a regular part of their function, and ultimately, it is malfunctions of that system which shifts the cells to cancer.

However, even dividing cells tend to do wildly different jobs, using very different ranges of genes.  This has to affect what their ultimate potentials are as cancers, and likely explains why, for example, prostate cancer (one type, at least) progresses very slowly, or brain cancer cells rarely develop mobility.  It might explain differential responses to treatment as well.

As cancer progresses, the cells tend to be more and more damaged.  Many of the cells will be too damaged to live, but the damage will also produce mutations that unlock abilities that are in the genes but that the original cells did not use.


The evolutionary process.

Simply put, the natural selection part of evolution works at the individual level – in this case, individual cancer cells survive and make copies of themselves – but plays out on the population level.  It’s the entire population of cancer cells that has its effects on the body.  The body is a fairly friendly place for its own cells, but a tumor changes its own environment in bad ways, and then treatments change the environment dramatically.  The progression of a cancer is a dance between what the tumor as a whole needs and what particular mutated cells in the tumor can do.  The cells that can handle changes persist and reproduce while many around them die.

Ultimately, a population of cancer cells kills its ecosystem (unless it’s Tasmanian devil snout cancer), but evolution isn’t about the endgame;  the dinosaurs were doing pretty well when that asteroid dropped on them.


The steps.

A cell is a complex place dealing with internal and external signals that control what they do and when they do it.  Dividing cells divide when they need to and then settle down and do their job.  They respond to chemicals released by neighboring cells, or chemicals in the tissue fluid, or chemicals carried in from the blood.  Damaged cells have ways of checking their damage levels and refusing to divide.  Often, damaged cells activate a process called apoptosis, during which they purposely kill themselves.

In cancer, cells divide that shouldn’t, and they keep dividing.  It may be that the interplay that switches from “division” to “do your job” malfunctions.  Maybe the response process to begin a division goes bad.  Maybe a damaged cell does not kill itself, giving rise to more damaged cells.  Maybe the system that checks for damage is itself damaged.  These and many other problems can be the initial trigger for a change to cancer.

Often, early cancer cells try to do their jobs, but they are not very good at it.  The cells that don’t try a shift in cell chemistry, that just plow on to another division, are doing a simpler process and are probably more likely to survive.  Over time, a tumor often loses distinctions that identify the tissue it started as.  The cells start to look like early embryo cells, another population that is purely in the business of making more cells.  A tumor grows, using body resources but giving nothing back.

There is evidence that the immune system may be cued to recognize and destroy cells that have become cancerous.  Cells that retain the cellular markers that the immune system recognizes get destroyed.  If a cancer cell does not express those markers, it doesn’t use those genes, the immune system leaves it alone.  That is an early evolutionary step for a “successful” cancer.

Cells in the mass that are the most efficient dividers are the most likely to dominate in a growing tumor;  genes that aid in division are likely to be activated.  Telomerase, an enzyme that helps in the production of new chromosomes leading into a division, often is produced more in these cells.  As we age, lack of telomerase has been associated with inability to divide cells to repair damage.  Anti-aging treatments that boost telomerase may help early-stage cancers to get going.

As a tumor grows, the cells on the inside of the mass get isolated from passing blood vessels.  In some tumors, cells activate a gene for a signaling molecule that causes blood vessels to grow into the tumor;  this molecule is useful during our growth phases, but as adults we stop using it.  One class of cancer drugs counteracts this signal.  However, in some tumors, the ability to survive low-oxygen, low-nutrient conditions, features found in muscles and skin, activates.  Cells that can’t survive the conditions die.

Radiation can be aimed at local tumors.  Radiation is absorbed by DNA, shaking and breaking it.  The broken DNA is often misrepaired, strengthening the signal to resist new divisions, and when divisions do happen, distribution of loose pieces may cause the death of the daughter cells when they activate genes on extra or missing pieces.  Radiation at this strength also can very badly affect our normal cells;  multiple lower-strength beams are aimed to overlap at the tumor location and have lesser effects on the cells hit on the way in and out.  Radiation is not an option for cancer that has spread through the body.

Chemotherapy has effects mostly on the chemistry active in dividing cells.  The side effects come from how it works on our normal, dividing cells, like those lining our digestive systems or hair follicles.  Is it possible for the molecular target in one or more cancer cells to be unaffected?  Yes, which means that unaffected cell or cells will survive and give rise to a chemotherapy-resistant mass.

In some of the tumor cells, genes are activated that would normally be in use in white blood cells or some repair cells, giving those cells the ability to detach from the mass and crawl away.   This is the shift to malignancy or metastasis, probably the most dangerous change that can happen.  Loose cells move away from the original site.  Inside spaces such as an abdominal cavity, they might float about the space and settle elsewhere;  in many places, they spread the same way that white blood cells do, moving into the lymph drainage system as a way into the blood circulation.  That creates spreading patterns for various malignant cancers.

Spreading cancer cells settle in other sites and divide, forming new tumors.  These tumors sap the body’s resources more and more, depleting other tissues.  Do they mobilize nutrients from other tissues from afar, the way that fetuses can commandeer nutrients from the mother?  Do nutrition-based treatments bolster the body’s ability to resist these effects?  In any case, eventually either the treatments manage to destroy most or all of the cancer cells or the cancer outcompetes critical body systems, starving them.


What’s it all mean?

This is just another way to look at a massive problem.  It may be a useful perspective in terms of treatment, or it just may be a way to understand the progress of cancer.  Recently, a massive genetic study of cancers found that, no matter what the starting tissue, advanced cancers tended to have activated the same array of genes.  From an evolutionary standpoint, this is convergent evolution:  descendants from different ancestors, adapting to the same conditions, often evolve the same answers to shared challenges.

An evolutionary perspective does appear in some cancer research, but it does not seem to be a big part in treatment or education about the disease.  I’m not a researcher (I’m a parasite biologist, which is why I tend to look at cancer and see an adapting invader), but I am an educator, and I hope that this webpage adds to available information.





Copyright 2013, 2016, Michael McDarby.

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