Some cancer therapies may provide a new way to treat high blood pressure
Georgetown University Medical Center News Nov 23, 2017
Drugs designed to halt cancer growth may offer a new way to control hypertension, say Georgetown University Medical Center investigators. The finding could offer a real advance in hypertension treatment because although a number of high blood pressure drugs are now available, they work by different mechanisms that are not suited for all patients.
The study, published in the journal Hypertension, found that fibroblast growth factors, or FGFs, involved in increasing blood vessel growth so that cancer can grow, also have a systemic effect on blood pressure. The study suggests that just as oncologists use FGF inhibitors to control cancer, clinicians may be able to use FGF inhibitors to regulate blood pressure and control disease associated with hypertension.
ÂItÂs rare that a single class of drugs can be used for such different conditions, but that is what our study strongly suggests, said the studyÂs senior investigator, Anton Wellstein, MD, PhD, professor of oncology and pharmacology at Georgetown University School of Medicine and a researcher at Georgetown Lombardi Comprehensive Cancer Center.
Wellstein and his collaborators previously found that the FGF pathway, when switched on, drives growth of blood vessels that feed a growing tumor (angiogenesis). The development of FGF inhibitors is based in part on their ability to inhibit angiogenesis. The current study took a deeper dive into the pathway and found that a protein, FGFBP1, modulates FGF. The gene that produces FGFBP1 to regulate FGF is known as FGF binding protein 1.
Wellstein had learned from a publication by a group in the United Kingdom that a population in Eastern Europe that had hypertension also had a variation of the FGFBP1 gene. Due to this gene variation in these individuals, FGFBP1 was over-expressed in kidney tissue, the major control hubs for blood pressure.
He decided to test the link between FGFBP1 and hypertension in a mouse model his laboratory at Georgetown had created that revealed the link between FGF and cancer. In these mice, FGFBP1 can be switched on or off.
Wellstein partnered with Christopher S. Wilcox, MD, PhD, professor of medicine at Georgetown and the George E. Schreiner Chair of Nephrology, and when investigators switched on FGFBP1 in mice, their blood pressure shot up. ÂIt actually went up 30 mm Hg from a normal blood pressure to pretty bad hypertension, said Wellstein. ÂIt was amazing.Â
He adds that he turned the gene on Âjust to a level you see in people in the Eastern European group who have hypertension. Wellstein also clarified that when a cancer switches on overproduction of the FGF pathway, in order to stimulate blood vessel production, that has only a local tumor effect, not a systemic one. Most patients using cancer treatment have normal blood pressure, he said.
Further research revealed that hypertension regulation by FGFBP1 occurred in the resistance vesselsÂthe end portion of vessels in different tissues that control the flow to that tissue. The aberrant FGFBP1 gene increased the vessel response to a hormone (angiotensin II) that constricts the blood vessels, making blood pressure rise.
ÂFGF can control how sensitive the blood pressure regulation by angiotensin II is, said Wellstein. ÂThat tells us that if a person has hypertension, it is possible to target FGF signaling because it contributes to maintenance of high blood pressure by altering sensitivity to a major vasoconstrictive hormone, angiotensin II, he said.
Investigators then used an FGF inhibitor in mice with a switched on FGFBP1 gene, and found the drug effectively lowered the sensitivity to angiotensin II in several vascular beds.
ÂOf course, we canÂt say that this tactic will work in humans with hypertension, but it will be straightforward to test this rather surprising possibility to target a new mechanism of blood pressure control, said Wellstein.
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The study, published in the journal Hypertension, found that fibroblast growth factors, or FGFs, involved in increasing blood vessel growth so that cancer can grow, also have a systemic effect on blood pressure. The study suggests that just as oncologists use FGF inhibitors to control cancer, clinicians may be able to use FGF inhibitors to regulate blood pressure and control disease associated with hypertension.
ÂItÂs rare that a single class of drugs can be used for such different conditions, but that is what our study strongly suggests, said the studyÂs senior investigator, Anton Wellstein, MD, PhD, professor of oncology and pharmacology at Georgetown University School of Medicine and a researcher at Georgetown Lombardi Comprehensive Cancer Center.
Wellstein and his collaborators previously found that the FGF pathway, when switched on, drives growth of blood vessels that feed a growing tumor (angiogenesis). The development of FGF inhibitors is based in part on their ability to inhibit angiogenesis. The current study took a deeper dive into the pathway and found that a protein, FGFBP1, modulates FGF. The gene that produces FGFBP1 to regulate FGF is known as FGF binding protein 1.
Wellstein had learned from a publication by a group in the United Kingdom that a population in Eastern Europe that had hypertension also had a variation of the FGFBP1 gene. Due to this gene variation in these individuals, FGFBP1 was over-expressed in kidney tissue, the major control hubs for blood pressure.
He decided to test the link between FGFBP1 and hypertension in a mouse model his laboratory at Georgetown had created that revealed the link between FGF and cancer. In these mice, FGFBP1 can be switched on or off.
Wellstein partnered with Christopher S. Wilcox, MD, PhD, professor of medicine at Georgetown and the George E. Schreiner Chair of Nephrology, and when investigators switched on FGFBP1 in mice, their blood pressure shot up. ÂIt actually went up 30 mm Hg from a normal blood pressure to pretty bad hypertension, said Wellstein. ÂIt was amazing.Â
He adds that he turned the gene on Âjust to a level you see in people in the Eastern European group who have hypertension. Wellstein also clarified that when a cancer switches on overproduction of the FGF pathway, in order to stimulate blood vessel production, that has only a local tumor effect, not a systemic one. Most patients using cancer treatment have normal blood pressure, he said.
Further research revealed that hypertension regulation by FGFBP1 occurred in the resistance vesselsÂthe end portion of vessels in different tissues that control the flow to that tissue. The aberrant FGFBP1 gene increased the vessel response to a hormone (angiotensin II) that constricts the blood vessels, making blood pressure rise.
ÂFGF can control how sensitive the blood pressure regulation by angiotensin II is, said Wellstein. ÂThat tells us that if a person has hypertension, it is possible to target FGF signaling because it contributes to maintenance of high blood pressure by altering sensitivity to a major vasoconstrictive hormone, angiotensin II, he said.
Investigators then used an FGF inhibitor in mice with a switched on FGFBP1 gene, and found the drug effectively lowered the sensitivity to angiotensin II in several vascular beds.
ÂOf course, we canÂt say that this tactic will work in humans with hypertension, but it will be straightforward to test this rather surprising possibility to target a new mechanism of blood pressure control, said Wellstein.
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