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A combination of drugs that target oestrogen production may help prevent lung cancer, according to research presented at the AACR-IASLC (American Association for Cancer Research – International Association for the Study of Lung Cancer) joint conference.
The conference, ‘Molecular Origins of Lung Cancer: Biology, Therapy and Personalised Medicine’, was told that anti-oestrogens significantly reduced the number of tobacco carcinogen-induced lung tumours in mice during a preclinical study.
“Anti-oestrogens have been shown to prevent breast cancer in some women,” explained Jill Siegfried, Professor of Pharmacology and Chemical Biology at the University of Pittsburgh Cancer Institute.
“If anti-oestrogens can prevent lung cancer as well, this would be a major advance, because these drugs are safe to give for long periods and there are no approved ways to prevent lung cancer.”
Most lung cancers are positive for a type of oestrogen receptor that makes lung tumours grow when exposed to oestrogen, while aromatase in the lungs also produces oestrogen.
Siegfried and colleagues hoped that by blocking this oestrogen receptor and the aromatase enzyme, they might be able to prevent oestrogen-sensitive lung tumours.
To test this theory, they conducted a study on two groups of female mice: one group that was currently being exposed to a tobacco carcinogen and one that had past exposure to a tobacco carcinogen and in which some precancerous cells had already formed.
The mice were assigned to treatment with a placebo, the aromatase inhibitor anastrozole, the antiestrogen fulvestrant or a combination of anastrozole and fulvestrant.
“The first model asks whether the treatments inhibit the process by which cancer is first started before it is even detectable under the microscope, and the second asks whether the treatments inhibit the process by which microscopic pre-cancers develop into visible tumours,” Siegfried said.
In the first model, the combination treatment given during carcinogen exposure resulted in significantly fewer lung cancer tumours compared with placebo or either treatment alone.
The tobacco carcinogen was stopped once treatment began to maximise its ability to halt lung cancer development. Combination treatment also resulted in maximum antitumor effects in the second model, where precancerous cells were already present.
According to Siegfried, these results suggest that anti-oestrogen treatment combined with an aromatase inhibitor prevents lung cancer development during tobacco carcinogen exposure and after carcinogen damage to the airways has already occurred.
Siegfried said that ultimately, the hope is that this research could lead to an approved treatment that could greatly reduce the risk for an ex-smoker to develop lung cancer.
“We may be able to prevent lung cancer in people who have been previously exposed to tobacco carcinogens using some of the same anti-oestrogen drugs that can prevent breast cancer,” Siegfried said.
“A lot of work needs to be done to determine who would benefit from this therapy, and these drugs would need to be tested in clinical trials in those at high risk for lung cancer.”
American Association for Cancer Research
