Bone Drugs May Thwart Development of Cancer ‘Seeds’

What do cancer cells and seeds have in common? The way that they spread to a new site and germinate it seems.

When a plant goes to seed, its seeds are carried in lots of different directions, but they can only grow and develop if they land on soil which is conducive to growth. Similarly, it is now well known that when cancer spreads secondary tumors (or metastases) do not develop by chance, as some organs provide a more fertile soil for tumor growth than others. These ideas form a long-running hypothesis in cancer research called the ‘seed and soil’ hypothesis.

A recent editorial in the Journal of Clinical Oncology this week by Dr Michael Gnat, further reinforces this hypothesis for cancer development, and that a certain group of bone cancer drugs, bisphosphonates, might create an “unfavorable soil” in which the development of cancer cells is thwarted.

Bisphosphonates are the treatment of choice for preventing bone loss and fractures in postmenopausal women with osteoporosis. They are also being investigated as treatment for preventing cancer-induced bone loss in women with early-stage breast cancer. Importantly, they have demonstrated anti-cancer activity in the lab and in clinical studies, which have shown that they:  block the release of factors that promote tumor growth and angiogenesis (growth of the tumors blood supply), induce cancer cell death (or apoptosis), prevent cancer cells sticking to each other, reduce the ability of cancer cells to spread via blood vessels, and activate the immune system to attack cancer cells. 

Based on this background information, several studies have been set up to determine whether bisphosphonates given to women with postmenopausal osteoporosis may reduce the risk of breast cancer, including two studies reported in the same issue of the Journal of Clinical Oncology.

In the first study by Chlebowski et al., approximately 150,000 women who received bisphosphonates for osteoporosis had a 32% reduction in the risk of breast cancer versus those who did not receive bisphosphonates. In a separate study by Rennert et al., a 28% reduction in the risk of breast cancer was reported in women receiving bisphosphonates for more than 1 year.

‘At this point, it would be premature to recommend the use of oral bisphosphonates to prevent breast cancer in all postmenopausal women. However, it is not unreasonable to consider the potential anticancer benefits of bisphosphonate therapy’

However, these results should be considered with caution as the authors note that several factors may have influenced the results, including age, ethnicity, and tobacco use to name but a few, says Dr Gnat. As a result, he states, ‘these analyses should be viewed as hypothesis generating and not practice changing at this time’…. ‘At this point, it would be premature to recommend the use of oral bisphosphonates to prevent breast cancer in all postmenopausal women. However, it is not unreasonable to consider the potential anticancer benefits of bisphosphonate therapy, in addition to its bone protecting effects’.

‘Bisphosphonate-induced changes to the microenvironment surrounding potential cancer cells can be exploited in preventing cancer’

Dr Gnat also states ‘The statistically significant reductions in breast cancer risk associated with bisphosphonate use “are profound and intriguing, because they suggest that bisphosphonate-induced changes to the microenvironment surrounding potential cancer cells can be exploited in preventing breast cancer,”. He goes on to say that these significant results are ‘profound and intriguing’ as they ‘suggest that bisphosphonate-induced changes to the microenvironment surrounding potential cancer cells can be exploited in preventing cancer’. He also suggests that these results support the idea that the seed and soil hypothesis is relevant to both healthy postmenopausal women as well as in preventing recurrence in women with early-stage breast cancer.

In conclusion, Dr Gnat suggests that future anticancer treatments may target the tumor microenvironment in addition to the cancer cells themselves.

References:

1. http://jco.ascopubs.org/cgi/content/full/28/22/3548

2. http://jco.ascopubs.org/cgi/content/abstract/28/22/3577

3. http://jco.ascopubs.org/cgi/content/abstract/28/22/3582

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One response to “Bone Drugs May Thwart Development of Cancer ‘Seeds’

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