Potential new lung cancer drug shrank tumors in mice

Potential new lung cancer drug shrank tumors in mice

Researchers in the UK working with a new experimental drug for lung cancer showed that it eliminated small cell lung cancer tumors in 50 per cent of mice and also stopped tumors from growing and becoming resistant to treatment. The researchers now plan to do clinical trials to test whether the drug might be able to help people with small cell lung cancer, which can't be treated with surgery because it spreads so fast.

The study was the work of corresponding author Professor Michael Seckl and colleagues and was published online in the journal Cancer Research on November 10. Seckl heads the Molecular Oncology and Lung Cancer Research Sections at Imperial College London.

Lung cancer is the most common cause of cancer death in the world. In the UK, around 100 people are diagnosed with lung cancer every day, and about 1 in 5 of them will have small cell lung cancer, for which the survival rate is very low: only 3 per cent of patients with small cell lung cancer are expected to live more than 5 years after diagnosis.

In small cell lung cancer the tumors spread so fast it's rarely feasible to remove them surgically, and although they respond at first to chemotherapy, with or without radiation, the tumors soon become resistant to treatment and grow back rapidly.

The researchers at Imperial College London had already discovered that small cell lung cancer tumour cells proliferate faster because they are fuelled by a growth hormone called FGF-2, which also triggers a survival mechanism in the cancer cells that makes them resistant to chemotherapy.

For the current study, they went a step further and tested the effect of an experimental drug called PD173074, which blocks the receptor via which FGF-2 attaches itself to the tumor cells.

PD173074 was first developed in 1998 as a way to to stop tumours from forming blood vessels around them. This new study is the first to show it has a therapeutic effect in mice.

Seckl and colleagues first tested the drug "in vitro", ie in "test tubes" containing cells taken from human tumors. They found that the drug stopped the cancer cells from proliferating and prevented FGF-2 from triggering their survival mechanism, making way for them to be killed with standard chemotherapy drugs.

Then they tested the drug "in vivo" on live mice with two different types of human small cell lung cancer tumours.

In a first test on mice, they found that the drug on its own eliminated tumors in 50 per cent of the animals and the mice remained disease-free for at least one year.

In a second, separate test on mice, they found that the drug also enhanced the effect of standard chemotherapy. The chemotherapy drug the researchers used was cisplatin, which is frequently used to treat patients with the disease.

They found that both PD173074 and cisplatin alone slowed down tumour growth, but when the drugs were combined, they slowed down tumour growth significantly faster than either drug on its own.

The researchers also found that the effect of PD173074 was dose-dependent: the more drug they added, the less the cells proliferated.

And using PET scans, they showed that the drug reduced DNA synthesis in the tumor cells, an indicator of inhibited cell proliferation.

Seckl and colleagues also found that the rate of apoptosis or cell suicide in the tumors went up after the mice received the drug.

Seckl told the press that:

"We urgently need to develop new treatments for this disease. Our new research in mice suggests that it may be possible to develop the drug PD173074 into a new targeted therapy for small cell lung cancer."

"We hope to take this drug, or a similar drug that also stops FGF-2 from working, into clinical trials next year to see if it is a successful treatment for lung cancer in humans," he added.

Seckl also explained that an added bonus of the drug was that it could be taken orally, making it less invasive than some other types of cancer therapy.

"The Fibroblast Growth Factor Receptor Inhibitor PD173074 Blocks Small Cell Lung Cancer Growth In vitro and In vivo.

Olivier E. Pardo, John Latigo, Rosemary E. Jeffery, Emma Nye, Richard Poulsom, Bradley Spencer-Dene, Nick R. Lemoine, Gordon W. Stamp, Eric O. Aboagye, and Michael J. Seckl.

Cancer Research, Published online first on November 10, 2009.

DOI: 10.1158/0008-5472.CAN-09-1576

Source: Imperial College London.

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