Follicle-stimulating hormone (FSH) is a molecule that is typically associated with the growth and development of ovarian follicles. However, in a recent study published in the New England Journal of Medicine, researchers explored whether the FSH receptor is also found in the blood vessels that feed a variety of human tumors. The rationale for this study was the observation that although FSH receptors are most commonly found in ovarian granulosa and testicular Sertoli cells, low level expression has also been seen in the endothelial cells that line the ovarian and testicular blood vessels. This prompted them to ask whether the FSH receptor might aberrantly be found in other blood vessels during times of tumor growth.

Ghinea, et al studied tissue from 1,336 treatment-naïve patients with a variety of tumor types. Using a combination of antibody and in situ hybridization techniques, combined with electron microscopy, they initially examined FSHR expression in prostate tumors that formed in mice, they found strong expression at the blood vessel endothelial cells found at the periphery of the tumors, and never in normal prostate tissue. They then expanded their search to a wide variety of paraffin-fixed human tumor types, including breast, colon, pancreas, bladder, kidney and lung. Without exception, FSHR expression was found in the blood vessels at the periphery of the tumor, and again not in normal tissue. They also examined FSHR in a variety of inflammatory states such as chronic pancreatitis, and did not regularly see FSHR, suggesting that this finding is reasonably tumor-specific.

The clinical implications of these findings is that the FSHR receptor may be an important target for both tumor imaging as well as treatment. From an imaging standpoint, because the receptor is most densely expressed at the tumor periphery, it implies that in vivo identification of the FSHR may provide a novel, very specific way to delineate the normal versus tumor tissue boundary, which would vastly improve our ability to stage tumors preoperatively and non-invasively. The molecular implications of FSHR expression on tumor vessels is not yet clear, but one intriguing observation is that the binding of FSH to its receptor leads to an upregulation of HIF-1alpha, which in turn upregulates the VEGF that is necessary for tumor angiogenesis. This makes it logical to consider therapies that aim to simultaneously block FSH and VEGF signaling. While very early days, this study adds yet a new marker and target to the growing number of molecular abnormalities in cancer.

I came to the Massachusetts General Hospital (MGH) in November 1999 having been Chair of the Department of Medicine and then Dean for Research at Tufts University School of Medicine, to develop strategic international programs to improve healthcare, after a long career in infectious diseases and immunology. Nine months later, my wife was diagnosed with ovarian cancer, so my personal war on cancer began.

As an immunologist involved in infectious diseases research, I set out to develop a better cancer therapeutic, one that would harness the immune system to attack tumors in patients already diagnosed with cancer, like my wife. We developed in my laboratory at MGH and patented a molecule named after my wife Janet called a Jantibody. This molecule combines the targeting of monoclonal antibodies with the punch of lymphocytes that can reject an organ transplant-or, I hoped, - a tumor. MGH subsequently licensed this new molecule to our new startup company, Boston BioCom LLC.

Simultaneous with our MGH lab work, we scoured Russia for both the purposes of an MGH- US State Department grant, and also my own personal war on cancer. At a military hospital in St. Petersburg, entirely closed to the outside world, we discovered unique Russian work on lasers, and specifically its application to enhance cancer vaccines.

Ultimately, what was developed in my laboratory and what we found in Russia was deemed valuable enough by Partners Healthcare System, the not-for-profit organization of the Harvard Medical School teaching hospitals, to help us form Boston BioCom LLC, in which Partners Healthcare System maintains an equity partnership stake. With Partners behind us and our exciting science, we were able to attract Pfizer to invest $10 million, becoming our largest partner, in March 2008. That is when the clock really started on advancing our science. I am the Chief Scientific Officer of the company.

Since 2008, we have built a vaccine focusing on a specific target common to ovarian cancer, pancreatic cancer, lung cancer and several others (our initial target, before Pfizer, was restricted to ovarian cancer). Our vaccine takes the best of monoclonal antibodies to target a tumor, while having the punch of killer T cells to reject the tumor as if it were a bad organ graft We have engineered the genes, made the proteins in a variety of different forms, created a second-generation vaccine that is also in the pipeline, and we now have definitive proof-of-concept that our vaccine stops the progression of ovarian cancer in mice. The survival data in mice is black and white. Our therapeutic vaccine works better than the standard toxic chemotherapy, platinum, when put into mice with ovarian cancer. We have an effective therapeutic for ovarian cancer that we can target to many other cancers as well. If even a fraction as effective in man, when licensed it could be used to target multiple other types of tumors with minor modifications. The Department of Defense thought enough of this technology to invest $1 million in supporting this research, where it can also be used against infectious diseases.

Another technology we have is a first-in-world laser technology that employs entirely novel physical parameters of the laser to nondestructively stimulate cells in the skin to produce a cell stress response. This "alarm" to the cells focuses immune cells at the site, and the result is that it multiplies the potency of every vaccine tested from 400-3,000%. Again, the Defense Department has been sufficiently interested in this technology to invest approximately $400,000 in its development. What we have also uncovered at the Massachusetts General Hospital and Harvard Medical School has multiple other uses for this nondestructive energy that stimulates cells. We can use our specific laser parameters to increase healing. I hasten to add that this laser light could be used through an endoscope or any catheter.

We are in the process of raising additional funds for the company to move these therapies to clinical trials.