Wednesday November 11 2009
The cells tested were from an aggressive form of lung cancer
“A new pill that could cure one of the most lethal forms of cancer is being developed by scientists,” reported The Daily Telegraph. The newspaper said that the treatment works by blocking the growth of the cancer cells and eventually causing them to self-destruct.
The researchers found that the drug, known only as PD173074, eliminated tumours in 50% of mice that were genetically engineered to develop the disease. The drug is designed to block the action of a hormone called FGF-2, which encourages the growth of small cell lung cancer. Surgery is not possible on this quick-spreading cancer, but chemotherapy and radiotherapy can initially reduce the tumour size. Theoretically, by blocking the hormone, the drug could make tumours more vulnerable to these treatments.
This is promising research, but the potential treatment is in its early stages and it is difficult to say when a drug that is developed from this research might be available. Further trials in animals will be needed before it can be tested in humans, and many drugs that appear to be effective in animals do not work in humans.
Where did the story come from?
This research was carried out by Dr Olivier E. Pardo and colleagues from the Cancer Research UK Laboratories and Clinical Sciences Centre at Imperial College London and elsewhere. Cancer Research UK and the Department of Health provided grant support. The study was published online in the peer-reviewed journal Cancer Research.
Most newspapers that reported this study have stressed the early nature of the animal research and the importance of finding better treatments for this lethal disease. The Daily Express says that “the tests offer hope that a cure could be on the horizon.”
What kind of research was this?
This laboratory research was conducted in mice. The researchers explain that small cell lung cancer (SCLC) accounts for 20% of all lung malignancies and that the disease recurs rapidly after a phase of initial treatment, after which it is usually resistant to further therapy. Overall survival rate is less than 5% three years after diagnosis.
There were several parts to this study. Researchers looked at the effect of a drug called PD173074 on cells from human tumours in the laboratory. They also studied the effect of the drug on two different types of human small cell lung cancer tumours that were grown in mice. This is known as a ‘mouse model of SCLC’ and is a common process for early drug development which can demonstrate if a drug has a therapeutic effect.
What did the research involve?
The drug PD173074 was first developed in 1998 to stop blood vessels from forming around tumours. The drug works by blocking the action of a hormone called fibroblast growth factor (FGF-2), which encourages the growth of these blood vessels. The researchers hoped that by blocking the action of the hormone, the tumour cells would die.
In the laboratory part of the study, the researchers looked at SCLC tumour cells in the test tube and observed how well they grew and became resistant to chemotherapy with and without the addition of the new drug.
They then tested the drug in two mouse models of SCLC. In one model, tumour cells were injected under the skin of mice. Once the tumours had grown to a measurable size, the animals were randomised to receive either PD173074 or no treatment for 28 days. In the second model, mice were also given intravenous injections of cisplatin, the usual chemotherapy agent for this disease, on days one and ten. The researchers counted the number of tumour cells affected by the new drug and also tested its effect in combination with standard chemotherapy.
In a third part of the research, the researchers used PET scanning on the mice. This imaging technique shows up fast-growing tumours as hot spots on the scan. It can be used to monitor the spread of the disease and how it responds to therapy.
What were the basic results?
The new drug stopped the cancer cells from growing and also prevented the hormone FGF-2 from triggering their survival mechanism. This meant the cells could be killed with standard chemotherapy.
The new drug also stopped cancer cells from proliferating and from becoming resistant to treatment in mouse models. In one animal model of small cell lung cancer, the drug eliminated tumours in 50% of the mice. In a second, similar mouse model, the drug enhanced the effect of standard chemotherapy.
When the drugs were combined, they slowed down tumour growth significantly faster than either drug on its own.
In the scanning part of the study, PET scans showed that treatment reduced DNA synthesis in the tumours. This indicates that the drug prevented the tumour cells from replicating. The researchers also found that the rate of cell death in the tumours increased after the drug was given to the mice.
How did the researchers interpret the results?
The researchers say that inhibiting the FGF-2 hormone, while improving the effectiveness of classic cancer therapy, might be efficient in a subset of lung cancer patients when used on its own.
This early research has shown, for the first time, a large effect of a novel drug in reducing the growth of SCLC tumours in mice. This is early research, but its results are promising and will probably lead to much interest in this class of drugs. Some strengths of this study should be noted:
- The effect of the drug was dose-dependent, which means the more drug the researchers added to the cells, the less the cells proliferated. This makes it more likely that the drug has a direct effect on the cells.
- The combination of treatment and PET scanning in one study means that the response to the drug was tested in several ways, adding further confidence in the results.
Although it is early days for this new drug and too soon to be heralding a cure for lung cancer, progress through the next phases of animal and human research will be followed with interest. Only by further rigorous safety testing in animals, followed by human studies looking at different doses of the drug and the effect of combining it with other agents, will its role in cancer treatment be known.