The Sunday Express has run a front page story stating that scientists have made a major breakthrough in cancer treatment “after cracking the ‘code’ behind the disease.” Sadly the story is actually only based on an idea rather than on concrete scientific evidence.
The story comes from a paper in the Journal of Translational Medicine written by Professor Michael Quinn and his team in Melbourne, Australia, back in November 2009. The paper focuses on a molecule called C-reactive protein (CRP), produced by liver and fat cells.
Importantly, the paper doesn’t detail the results of new scientific experiments,although the authors do discuss some preliminary data. Instead, it is an overview of previously published research.
What is CRP and why is it relevant to cancer?
Our bodies produce CRP during biological stresses such as inflammation. It circulates in the blood and sticks to ‘nasties’ such as bacteria or damaged cells, helping to flag their presence to the immune system for destruction. Under normal circumstances, CRP is only present in our blood at low levels; they rise sharply during inflammation, then fall quickly afterwards.
Increased levels of CRP have been found in people with several forms of cancer, including melanoma, ovarian, bowel and lung cancer. But generally, CRP measurements in cancer patients have only been taken at one point in time, or several weeks or months apart. This makes it difficult to conclude how CRP levels are affected by having cancer, or being treated for cancer.
In their journal article, Professor Quinn describes how his team measured CRP levels in melanoma and ovarian cancer patients every few days, and found that they cycle up and down roughly every week. The team show some of the results from these tests, but from only two patients.
But they don’t include any information about their methods, such as the number of times measurements were made, how many people they studied, how and when they took the measurements and so on. And there’s no mention of how CRP levels cycle in people without cancer by comparison – in scientific terms, there are no controls.
In the paper, the researchers say:
“The displayed data are from studies of single patients, and formal correlation between the CRP levels, cycles and clinical responses needs to be performed in larger numbers of patients before generalised conclusions can be applied.”
In other words, these results are extremely preliminary.
Going beyond their results, the scientists argue that the cycles in CRP levels are due to the ebb and flow of cell production by the immune system. They suggest that at times when CRP levels are low, the production of cells known as “effector” T cells is high. These are the workhorses of the immune system, produced from a type of cell called a T helper cell. Effector T cells produce special chemicals that help the immune system to fight infections and inflammation, including destroying dead or dying cancer cells that result from treatment. And immunotherapy techniques, such as treatment vaccines, can harness T cells to directly target cancer cells.
On the flip side, the researchers argue that when CRP levels are high, other immune cells cells known as “regulatory” T cells are produced. These cells dampen the cancer-fighting abilities of the “effector” T cells.
Linking CRP levels to treatment response
Professor Quinn and his team go on to suggest that levels of CRP are linked to how well a patient responds to treatment. As evidence, the researchers measured CRP levels at the same time as patients received treatment. The paper shows preliminary data from two people with melanoma – one who was given chemotherapy, the other treated with an experimental vaccine-based treatment. Again, no details are provided of the methods or the treatments.
The scientists suggest that the patient receiving the vaccine got most of their doses (16 out of 30) at ‘low’ points in their CRP cycle (i.e. the times when CRP levels were lowest). This patient had a “good response” to the treatment – though no clinical details are given, and we don’t know how they compare to other patients receiving the same treatment. But they also received 14 doses of vaccine at other times in the cycle – that’s nearly half. So it’s hard to be sure that the CRP cycle is having an effect on the patient’s response.
For the patient receiving chemotherapy, the data are even scarcer. CRP levels were measured at five points – three of which were close to the ‘top’ of the cycle (highest CRP levels), two about half-way down. This patient also apparently responded “well” to treatment.
Professor Quinn and his colleagues suggest that the vaccine is working because low CRP levels are encouraging effector T cells, which help the immune system to kill cancer cells in response to the treatment. In the case of the patient receiving chemotherapy, the researchers argue that the treatment is destroying regulatory T cells, which are multiplying rapidly when CRP levels are high. According to their theory, ‘knocking out’ these regulatory T cells when they are proliferating frees up effector T cells to get to work on cancer cells that have been damaged by the chemotherapy.
It’s a nice idea. But it’s fair to say that it’s just that – an idea. Based on the preliminary data in this paper, it’s impossible to say that it holds true for other cancer patients.
As a final point, the Express story mentions seven women with ovarian cancer who have been treated with chemotherapy according to their CRP cycle. But these experiments are not mentioned in the paper, so it is difficult to say whether there is a genuine effect.
It will be interesting to see the detailed, published results of the trial once it is completed. But until then, it’s impossible to say whether this is a significant advance in treatment for the disease.
Unfortunately this story doesn’t present any hard data, and it is too early to say whether the researchers’ theory will hold up in more detailed tests with a larger sample of patients.
“Breakthrough” is simply too strong to describe this work and it’s certainly not “the most exciting development since the introduction of chemotherapy in the Fifties”. The only real development here is the raising of false hopes for people with cancer and their families, and Professor Quinn and his team acknowledge themselves that their results are promising but preliminary.
The story – and the Australian news story on which it is based – retell the researchers’ speculation and early data as fact. There are also misleading descriptions of the treatment itself – for example, focusing on the drug as being given as a pill rather than by drip and claiming that it avoids “almost all the debilitating chemotherapy side effects.” The important part of the story is the timing of chemotherapy, not the drug itself (of which we have no details).
Finally, important caveats from Professor Quinn that were included in the press release have not been picked up more broadly. For example, he is quoted as saying “I don’t think this is the magic bullet yet but it’s certainly enough for us to continue our work.”
We know that the immune system plays an important role in cancer – Cancer Research UK is funding a number of projects in this area – and it may be that CRP levels do have something to tell us about a patient’s response to treatment. But based on the handful of preliminary data in this paper, it’s far too early to say.
Coventry, B. et al (2009). CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool? Journal of Translational Medicine, 7 (1) DOI: 10.1186/1479-5876-7-102</span
Pratim K. Ghose April 25, 2010
Well thought out comments. Good luck to research teams like Prof. Quinn’s.