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Is a new anti-angiogenic strategy on the horizon?

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As both a clinician and scientist, I always look at new biological findings with a mixture of enthusiasm and skepticism. In the New England Journal of Medicine, a very provocative finding was published (the Journal prides itself on being the first to report something that just might be a game changer). A new property of a well-known protein called the follicle stimulating hormone receptor (FSHR) was described – namely, its presence in the blood vessels of many different types of tumors in humans – breast, prostate, colon, and host of other cancers. Normally, FSHR is expressed in specific cells within the ovaries and testes, in keeping with its known roles in sex hormone production and menstrual cycle control. This was a very carefully done study, with multiple antibodies against FSHR and very careful analysis over the areas of many tumors and adjacent normal tissue. Staining for FSHR was seen in tumor-associated blood vessels within all of the tumor tissues in 1,336 cases, and in some cases of "precancerous" tissue. Its expression in blood vessels fell off progressively in moving away from the tumor into normal tissue.Might this new finding represent a target for treatment against many types of cancer? Well, we have been down this road before – a tumor-specific antigen that is hailed as a way to develop the perfect magic bullet, only to lead to disappointment once tested in patients. Still, anti-angiogenic therapy - the targeting of tumor blood vessels that are necessary for tumor growth and spread, has been a successful strategy, with the drug Avastin showing improvements survival in colon and brain cancer, but not fully curative in advanced cancers. In the case of breast cancer it delays progression without improving survival. Avastin does not only target tumor blood vessels, since the growth factor it targets is also involved in non-tumor blood vessel formation and other cellular functions – hence it has side effects. In the case of FSHR, the investigators showed that they can deliver particles bound to antibody to tumor blood vessels using animal tumor models. This might therefore represent a promising therapeutic avenue, although there may be toxicity to the ovaries and testes that would need to be addressed. It remains unknown why FSHR is expressed on tumor blood vessels – but there is good reason why it made the "scientific front page."

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