Common cancer link may unleash potential of antibodies and antiangiogenesis

The search for a magic bullet against cancer historically has glowed bright then dimmed, depending on the stage of discovery. Developments surrounding monoclonal antibodies and angiogenesis inhibitors have followed this cycle, as exuberance for their potential has bowed to the nuances that underlie the complex mechanisms on which they depend.

Now a new possibility promises to light the cancer scene, one that might allow oncologists to finally realize the full potential of monoclonal antibodies and angiogenesis inhibitors.

An international research team has found a link among common types and grades of cancer: extraordinarily high concentrations of follicle-stimulating hormone (FSH) receptors in the blood vessels feeding these cancers. The only normal blood vessels on which FSH receptors appear are those in reproductive organs and then only in much lower concentrations than the investigators found on the blood vessels that feed tumors.

The research done at the Mount Sinai School of Medicine in collaboration with France’s National Institute of Health and Medical Research and published in the Oct. 21 issue of the New England Journal of Medicine documented these high concentrations on blood vessel walls accompanying cancers of the prostate, breast, colon, pancreas, lung, liver, and ovary.

Ultimately, the discovery could lead to the development of new diagnostics in MR, PET, or even ultrasound imaging, the researchers say. There is also potential for developing highly specific anticancer drugs.

Built around antibodies specific to FSH receptors, tumor imaging agents might be injected into the bloodstream, where they would selectively bind to the new marker to visualize early tumors, according to Aurelian Radu, Ph.D., an assistant professor of developmental and regenerative biology at Mount Sinai. These antibodies might also carry therapeutic agents to the tumors. One of the chief active components of these therapeutic agents is an antiangiogenesis agent.

The concept underlying antiangiogenesis as a cancer therapy is to slow or stop the growth of blood vessels that feed new tumor growth, thereby starving the tumor. Such efforts, however, have been complicated by the general nature of and the body’s normal dependence on angiogenesis. The presence of FSH receptors promises to simplify oncology’s attack plan.

New therapeutic agents might be tagged with antibodies specific to FSH receptors. Once injected into the bloodstream, they might bind to the FSH receptor in such a way as to block release of the vascular endothelial growth factor that stimulates the growth of blood vessels. Antibodies specific to the FSH receptor might even carry coagulants that clog the vascular beds that surround existing tumors or destroy these blood vessels, according to Radu.

In the research that led to this possibility, the U.S.-French team evaluated tissue samples from the tumors of 1,336 people with any of the 11 most common cancer types and discovered high concentrations of FSH receptors on the blood vessels associated with all of these tissues. Using an animal model, the research team has since confirmed that agents coupled to FSH antibodies accumulate selectively on blood vessels that feed tumors, raising hopes that specific diagnostic and therapeutic agents can be developed.

Compared with currently available drugs, such agents promise not only to be effective but to have fewer side effects, because the target, the FSH receptor, otherwise appears in blood vessels found only in reproductive organs, and then only in much lower concentrations.