Tuesday November 10 2009
The darkened cells have become cancerous
Cervical cancer could be wiped out by “pioneering use of 'amazing' osteoporosis drugs”, the Daily Mail has declared. The newspaper says that drugs used to treat breast cancer and osteoporosis “eliminated the cancer in 11 out of 13 cases”. What it mentions only later in the article is that these 13 “cases” were mice.
This research gave an osteoporosis drug called raloxifene, a cancer drug called fulvestrant or no treatment to mice that were genetically engineered to develop cervical cancer when treated with oestrogen. The drugs reduced the incidence of cancer, but the authors of the research note that “further study is needed to determine whether this proposed model is relevant to human cervical cancer.”
The results suggest that these drugs may be worth investigating further for potential use in human cervical cancer. However, until human studies are carried out, it is not possible to say whether these drugs will play a role in the treatment of cervical cancer.
Where did the story come from?
Sang-Hyuk Chung and Paul Lambert from the University of Wisconsin School of Medicine and Public Health carried out this research. The study was funded by the National Institutes of Health in the US and published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences of the United States of America.
This story has been reported in the Daily Mail and Daily Mirror. The Mail states near the start of the article that one of the treatments “eliminated the cancer in 11 out of 13 cases”, but only later mentions that this was in mice rather than humans. The coverage in the Mirror article is very brief, but does point out that the research was in mice and quotes one researcher’s opinion that there are many similarities to how cervical cancer manifests itself in women and mice.
What kind of research was this?
This was laboratory research on mice, which looked at how cervical cancer is affected by drugs that block oestrogen receptors. Oestrogen receptors, known as ERs, are proteins that bind to the female hormone oestrogen. This allows the hormone to alter the way that the body interprets certain genes.
Early research into the effects of drugs needs to be carried out in animals before they can be tested in humans. This type of animal research can indicate whether a drug shows promise and is safe enough to try in humans. It does not guarantee that the drug will work or be safe in humans. Only subsequent human studies can establish this.
What did the research involve?
In this study, the researchers used mice that had been genetically engineered to develop a form of cervical disease. This resembled cervical disease associated with the human papilloma virus (HPV) in women, which can develop into cervical cancer.
Previous studies in these mice have shown that oestrogen must be present for cervical cancer to develop. They have also showed that the actions of the oestrogen receptor are key in the early stages of cervical disease, before the cells become cancerous. The researchers wanted to investigate whether drugs that block oestrogen receptors might be able to prevent or treat cervical cancer in these mice.
The researchers investigated two drugs, fulvestrant and raloxifene. Fulvestrant blocks all oestrogen receptors in the body, which results in menopausal symptoms in humans. Fulvestrant is currently used to treat breast cancer. Raloxifene is more selective in its effects, blocking oestrogen receptors in some tissues but not others. Raloxifene is used in the treatment of osteoporosis and has been trialled for the prevention of breast cancer in humans. The researchers say that it “has no major common side effects in women”. The British National Formulary lists possible side effects of raloxifene as hot flushes, leg cramps, peripheral oedema and flu-like symptoms.
In their first set of experiments, the researchers took the genetically engineered mice and treated them with oestrogen for six months to promote the development of cervical cancers. After this time, some of the mice were examined for cervical cancers, some received no further treatment for a month, some received fulvestrant injections for a month and some received raloxifene injections for a month. The researchers examined the effects of these different treatments on the presence of cervical cancers.
In a second set of experiments, the researchers looked at whether treatment with fulvestrant or raloxifene could prevent the development of cervical cancers in these mice. To do this, they treated the mice with oestrogen for six months, but also gave fulvestrant treatment during the fourth month of oestrogen treatment. At the three-month stage, the mice would have begun to develop precancerous cervical disease, but not cancer itself.
What were the basic results?
The researchers found that all of the six genetically engineered mice that had been treated with oestrogen for six months and then examined had developed cervical cancer. Eleven of the 14 mice (79%) that stopped receiving oestrogen treatment for a month still had cervical cancer at the end of this month.
Only one of the 13 mice (8%) treated with fulvestrant for a month had cervical cancer at the end of the month. None of the seven mice treated with raloxifene for a month had cervical cancer by the end of the month. This represented a statistically significant reduction in the proportion of mice with cervical cancer in those given fulvestrant or raloxifene compared to those left untreated for the month.
The researchers found that in six mice treated with oestrogen for three months, all had pre-cancerous cervical lesions at different stages of development, but none had cancer. Of the six mice treated with fulvestrant for a month at the three-month stage, none had pre-cancerous cervical lesions or cancer by six months.
How did the researchers interpret the results?
The researchers concluded that “these findings point to the potential value of ER antagonists in controlling gynecological disease in the lower reproductive tracts in women”.
This small study has shown that the oestrogen receptor blockers fulvestrant and raloxifene can treat cervical cancers in genetically engineered mice with this disease. Although these results suggest that the drugs may be worth investigating further for potential use in human cervical cancer, they may not represent the effects that the drugs would have in humans. As the researchers note, “Although our transgenic mouse model for HPV-associated cervical cancer recapitulates most aspects of human cervical cancer, it is obvious that further study is needed to determine whether this proposed model is relevant to human cervical cancer.”
HPV vaccination and screening programmes are likely to remain the best way of preventing this disease for the foreseeable future.