The Colors of Cancer

Or, where is the Golden Bullet?

Written by Thomas Hillen - August 07, 2019

There is a popular myth that the pharma companies have a Golden-Bullet-drug against cancer in their drawers and refuse to use it as to maximize profits. I will argue here that this is not true. Even more so, it is not even theoretically possible to have such a Golden Bullet drug against cancer. To make this argument, I invite you to join me in building a colorful picture of cancer in its many shades of paint.

There is a rich menu of cancer drugs out there which help to reduce pain experienced by patients, extend life, and increase the quality of life; however, drugs do not cure cancer! It usually comes back, sooner or later. There are only two ways to fully remove a tumor, and these are surgery and radiation treatment. If surgery completely removes cancerous cells, then the patient is healed. Similarly, if radiation burns the tumor out, then it is gone. My father, for example, had a lung tumor, which was detected early, removed right away, and he lives happily without any signs of recurrence. His surgery was followed by a period of chemotherapy, as is standard of care, just to be sure that no cancer cells escaped.

However, drugs are different than surgery and radiation, as drugs never kill all the cancer cells, and they produce huge side effects. We can roughly classify cancer drug treatments into three categories (i) chemotherapy, (ii) targeted treatments, and (iii) other treatments. Under other treatments I would mostly count new treatments, that are currently being developed, such as immuno-therapies, nano-therapies, and viral-therapies. All are promising new ideas and time will tell how effectively they can be used. In my blog here, I’d like to talk about the first two, (i) chemotherapy and (ii) targeted therapies, as these are established treatment methods that are commonly used.

The problem with cancer is the huge genetic diversity of its cells. Aggressive cancers show thousands of mutated genes, thousands of phenotypes, and an equal number of antigens. As we enter the realm of genomics, I’d like to offer an easy to understand analogy. Instead of talking about antigens, mRNA, proteases, antigen presenting cells, genotypes, phenotypes and all that omics language, I would rather talk about the color of a cell. Imagine that all healthy cells have colors in the range of blue, green, and yellow. There are many different cells in our body, and in a healthy tissue we expect a nice mixture of tones of blue, green, and yellow and every shade in between. If an external pathogen enters the body, for example a bright red bacteria, then the immune system can easily recognize it: kill all red cells!

Cancer is different. Cancer develops from our own cells, hence the first cancerous cells are also blue or green or yellow, maybe with a hue of red. Not enough red to trigger the immune response, however, so it can start growing. While growing it adds more diseased tones to the mix, a bit orange, a shade of brown, or maybe some more red. At this stage the immune system might activate and kill all cells that have too much red. Not bad, but it might already be too late to control the cancer and we need help from drugs.

As many patients will attest, chemotherapy hits you like a hammer. A broad-band cell killing agent is injected, which kills everything it encounters. The chemotherapeutic agent has been designed to kill more cancer cells than normal cells, and the hope is that the cancer is reduced while the side effects are still bearable. A cancer patient, Gabriel Flood (quota.com, April 18, 2017) found an interesting analogy:

“Chemotherapy is, metaphorically speaking, intravenous napalm that can and does burn cancer cells to death with startling efficiency”
Which have severe side effects …
“... often hit the Catch-22 of having to choose between being slain by the cancer or poisoned to a slower death by the chemo treatments.”
After all, the chemo has helped Gabriel Flood, and he has been cancer free for many years.

Let us integrate chemotherapy and targeted therapy into the picture of colored cells. Chemotherapy kills all cells that proliferate fast. In our image these are all cells with a dark color, dark red, dark green, dark blue, etc. This means, chemotherapy kills cancerous cells and also healthy cells. It reduces tumor burden but also has severe side effects such as indigestion, inhibited immune response, low blood cell counts, hair loss, etc. While, in our image, chemotherapy kills all the dark colored tumor cells, the light colored remain and continue to grow.

Targeted drugs are specifically designed to kill cells of one color, and one color only. For example assume patient A has a tumor that is dominated by pink cells. Then we take (or design) a drug against pink cells. Wow, it works like a charm, and the tumor size is reduced quickly, as all pink cells are gone. But what about the red, violet, brown, and orange cancer cells? These are left behind and grow into a recurrent tumor. The tumor shows drug resistance and we could continue to give the pink drug, but it would have absolutely no effect on the cancer any more.

Here is the conundrum of cancer drugs: They either kill everything in their way (chemotherapy), or they kill very specific cells (targeted therapy), which leads to resistance. What would a Golden Bullet drug have to do? The Golden Bullet drug would need to be able to identify all shades of red, violet, brown, and orange in a mixture of blue, green, and yellow. This seems very hard to do, and one drug alone will not be able to do the trick! Combinations of drugs seem necessary.

Combination therapies are very difficult to design. Most approved medicines are approved for single use only, and possible synergistic effects between drugs are only beginning to be studied. Some clinical trials consider combination of two drugs, but what we need might be drugs that act against 100s or 1000s of shades of color. Modern genomics gives us more and more information about the colors that are involved in a cancer. Genomics also shows that the color pallet of a cancer is different from patient to patient. What we need to develop in the future are rainbow-drugs. Drugs that are able to find all possible shades of cancer in human tissue, drugs that are multipotent, and drugs that are patient specific. A huge new research area of precision medicine opens up and it is far into the future until we have the first rainbow-drugs against cancer.

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