A Remarkable New Cancer-Fighting Discovery at Wake Forest – Angiotensin-(1-7)

“When you’re fighting cancer, you’re going to war against your body,” says Patricia Gallagher, PhD.

In the battle against cancer, which kills more than half a million Americans each year, Gallagher and Ann Tallant, PhD, both scientists at Wake Forest School of Medicine’s Hypertension and Vascular Research Center, have discovered a powerful line of defense that offers hope to save lives. In an ever-growing market of cancer therapeutics, they stand out as inventors of a dual fighting chemotherapeutic that they call “the aspirin of cancer drugs” because of its potency and simplicity to manufacture.

For decades, Gallagher and Tallant along with other investigators in the Hypertension and Vascular Research Center, have studied angiotensin-(1-7), more commonly called Ang-(1-7) – a small, but remarkable, peptide hormone made up of a string of seven amino acids. Although Ang-(1-7) is a natural compound that is normally found coursing through the human body, Gallagher and Tallant, in their early research, showed that, in elevated doses, it has remarkable anti-tumor healing powers and the potential to change the battlefield in the war against cancer.

Ang-(1-7) has the unique capability to fight cancer in two distinct ways – by directly inhibiting cell growth and restricting the blood supply to tumors through reduced blood vessel formation – without the unwanted toxicity of traditional chemotherapeutics. Even more, it has cardiovascular benefits, preventing fibrosis, or stiffening of the heart that can lead to heart failure.

“Aggressive cancers have incredible ways of evading compounds designed to prevent their growth,” says Tallant. “Ang-(1-7) targets more than just tumor cells. It destroys cancer from all fronts by attacking the tumor microenvironment, the blood vessels that feed tumors and the structures that it grows on.”

The Origins of Angiotensin-(1-7) Discovery

Like most great discoveries, Ang-(1-7) began as a simple idea. It didn’t start with a lunch napkin sketch or a boardroom discussion, but in a basic science lab at Wake Forest School of Medicine in the 1990s.

Gallagher, a molecular biologist, and Tallant, a cell biologist, had attended graduate school at the same time at the University of Tennessee at Memphis and were working together at Wake Forest, where they were studying angiotensin II, the primary regulator of blood pressure. They were curious to learn more about the characteristics of its sister peptide, Ang-(1-7), which is just one amino acid different.

“Our first study was done just for fun,” remembers Gallagher. “We’re cardiovascular people. The question about whether this had an effect on cancer? We did it to satisfy our own curiosity more than anything else. So, we ordered some lung and breast cancer cells, studied them in lab cultures and saw that Ang-(1-7) inhibited cell growth. It was the direct opposite of Ang II, which is a mitogen and promotes cell growth.”

Their discovery was published in Carcinogenesis (Gallagher, P. E. and E. A. Tallant (2004). “Inhibition of human lung cancer cell growth by angiotensin-(1-7).” Carcinogenesis 25(11): 2045-2052).

“We watched the story get picked up and go around the world,” says Tallant. “The phone started ringing with calls from cancer patients and their loved ones near and far looking for treatment.”

Gallagher remembers receiving a call from a man in Canada whose wife had stage IV breast cancer with metastases in the brain. “He had two young children. He was desperate, and there was nothing we could do at the time to help him and his family. It was tough. This was a turning point. I thought – we’re either going to do this, or we’re going to walk away now.”

“It was all very personal,” she says. “We all have family and friends that we’ve lost to cancer. Ann lost her mom to cancer when she was 17, and I lost my partner a few years ago. We didn’t want anyone else to have to go through this.”

Committed to a Cure with Ang-(1-7)

Following their initial discovery, the researchers studied the effects of Ang-(1-7) in a mouse model and saw that it inhibited the growth of lung and breast tumors. They then partnered with a team of physicians at Wake Forest Baptist’s Comprehensive Cancer Center to conduct a Phase 1 clinical trial, examining toxicity in 15 patients. The physicians were encouraged to see clinical benefits in four of 15 evaluable patients; one patient had a 19% reduction in tumor measurements and three additional patients had stabilization of disease lasting more than three months.

“More surprising, we discovered that the drug not only prevented cell growth but had limited toxicity,” says Gallagher. “In fact, more than half of the patients said that they felt better after treatment. This is most likely due to Ang-(1-7)’s cardiovascular effects. It’s an added benefit, a double whammy, that it is anti-fibrotic and anti-inflammatory, especially for patients who suffer with hypertension or cardiac problems.”

Tallant explains: “Most traditional cancer drugs cause harmful cardiac effects. This drug is different. It’s almost like a dimmer switch that brings the body’s natural protein levels back to normal and reduces tumor growth without damaging essential tissues. Compared with traditional chemotherapies, Ang-(1-7) is drastically different in that it keeps the patient’s quality of life intact.”

Dual, Targeted Chemotherapeutic Action

Destroying cancer takes more than just killing cancer cells. It takes an all-out attack on the tumor microenvironment – the surrounding cells, tissues, structures and arteries.

“Cancer isn’t just one big ball of tumor cells. There are all types of cells that are players – fibroblasts that provide the structure for growth, growth factors that cause tumor cells to divide and proliferate, and the blood vessels that feed the cancer,” explains Gallagher.

“Our drug has a unique dual fighting action, destroying the tumor and its environment from all sides,” says Gallagher. “It prevents the proliferation of cancer cells and blocks the formation of blood vessels, so that the cancer doesn’t have the blood supply to grow.”

But the real beauty lies in the fact that this cancer weapon, while targeting and wiping out deadly cells, protects healthy tissues that the body needs to function and thrive.

Future Directions

With a Phase 2 clinical study underway, Tallant and Gallagher are currently exploring the effects of Ang-(1-7) on many cancers, including prostate, brain and lung tumors and pediatric sarcomas. They are also interested in examining the drug as a non-toxic therapy for triple negative breast cancer.

They continue to explore partnerships with industry to advance the study of the drug on different types of cancer, with the hope of accelerating commercialization and getting Ang-(1-7) to market. “That’s our dream – to see Ang-(1-7) as a little bottle of pills available to cancer patients one day,” says Gallagher.

“But Mother Nature doesn’t give up her secrets easily,” Tallant says. “We’ve made great strides and are excited about our continued exploration and the possibilities for cancer treatment ahead.”

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