Researchers are constantly on lookout for new substances that are more effective and safer as cancer treatments than what is already available. In an ideal world it would be possible to know which substances would have effect on cancers and at the same time be safe. But the world isn’t perfect. So the researchers have to use some kind of experimental model to select substances that might be useful to patients. And they publish the results of these experiments.
Sharing experimental results through publication is a good thing. But it also opens up for all sorts of cancer quackery, where the results are used as definite proof that ideas of theirs work. And the fact that it is not used as conventional treatment is often claimed to be because of some kind of conspiracy. The internet is full of such bogus cures where the evidence consists of a combination of experimental studies and cancer cure testimonials. We could mention cannabis, antineoplastons (more correctly phenylbutyrate) and Graviola.
How good these experimental models are at predicting effects in humans is of no concern to promotors of cancer quackery. But researchers have asked themselves this question, and looked into it.
Before we look more deeply into the results of the researchers efforts we will side step a little and form an overview of the principles in these experimental models.
CANCER CELL LINES
A cancer cell line is simply a cell culture grown in a lab from single cell. A cancer in a patient is not a cancer cell line. There is great variation of the cells within a cancer. And the ways they interact with the surrounding normal cells are also very complex. The American National Cancer Institute (NCI) recommends that a panel of 60 cell lines reflecting different cell types and different drug resistance profiles in the most common types of adult cancers is used for drug screening.
TYPES OF MOUSE MODELS
Four different types of mouse models are used in the initial testing of potential new drugs:
1) Genetically engineered: The mice have specific genetic mutations that result in a high probability that they will develop specific types of cancers.
2) Mice injected with cancer cells originating from mouse cancers
3) Mice injected with human cancer cells under the skin
4) Mice injected with human cancer cells into the tissue that the cancers originate from
None of these models are exactly like human cancers as they occur in human patients, but they do make sense as models of various aspects of cancer.
HOW GOOD ARE MOUSE MODELS AT PREDICTING EFFECTS IN HUMANS?
Here is a research paper that looked into this question. The researchers looked at the relationship between response to 39 cytotoxic agents in mouse models and subsequent clinical phase II trials.
There was a positive response in a mouse model if the tumour was reduced in size by at least 60 % or the mouse survived at least 25 % longer than untreated controls.
There was a positive response in a clinical trial if the tumour was reduced in size by at least 50 % in at least 20 % of the patients.
This figure summarizes some important results:
Each bar represents one type of cancer that was tested in mice. The height of the bars illustrate how well the effects in mice correlated with effects in subsequent clinical trials. The “*” on top some of the bars indicate that the correlation was statistically significant, ie stronger than what would be expected from play of chance.
From looking at the figure we can readily see a few things:
1) Rarely did a positive response in a mouse model predict a positive response in the same kind of cancer in patients. Only in a lung cancer model did the response correlate to response in lung cancer patients (NSCLC = non small cell lung cancer).
2) Rarely did positive response in a mouse model predict positive response in other kinds of cancer in patients. If there was response in mice implanted with breast cancer, there were some response in patients with lung cancer, melanoma and ovarian cancer. And a positive response in patients with melanoma was also seen with drugs that showed positive response in mice implanted with colon cancer.
Another interesting figure is this one:
It shows that if a positive response was found in less than 1/3 of the cancer types in mice, it was unlikely to produce a positive response in human cancer patients.
THE “SUPPRESSED BUT PROVEN” CANCER CURES
The fact that the experimental mouse studies are published in well reputed peer-reviewed journals disproves that research into these things are being suppressed, so we won’t address this idea any further in this post. But let’s take a look at the experimental evidence of some of the “suppressed” cures that are out there:
A study found that THC reduced tumor bulk by only 50% in experimental mice implanted with only one type of cancer cell line. This is being touted widely by cancer quacks as evidence of efficacy of cannabis, but as we have seen it is not possible to draw such a conclusion. Here is an update on the current evidence on cannabis as a potential anti-cancer tool.
Proponents of Burzynski sometimes claim that this study is one that independently of Burzynski proves that antineoplastons work. It is a study involving mice with two cancer cell lines. What the researchers found was a reduced growth rate compared to controls. Not tumor shrinkage. It may be Burzynski independent, but proof it is not. As a side note the active ongoing research into clinical applications of sodium phenylbutyrate (which we now know is the precursor of Burzynskis antineoplastons) firmly disproves that research into this compound is being suppressed.
There are a few studies on cultured cell lines. But we did find one study on mice. Again the study involved only one cell line. And only reduced growth rate – not tumor shrinkage was seen.
We think a plausible explanation of why these natural substances have not caught the interest of the pharmaceutical industry is obvious. A substance with so little effect in experimental mouse models is not likely to be useful as cancer treatment. The research funds are better spend elsewhere.
Update: There is another good post about preclinical cancer research on Science-based medicine.