“My goal is to get to a permanent cure for cancer — where the cancer does not recur,” says Ramesh Rengan, MD, PhD, professor and chair of the Department of Radiation Oncology at the UW School of Medicine and past director of the Seattle Cancer Care Alliance Proton Therapy Center.

For over 100 years, the medical community has primarily recognized two ways to achieve a permanent cure to most solid cancers: surgically remove the tumor or use X-rays to radiate the cancer. However, both tools target only the cancer you see. What about the cancer that has spread to other parts of the body? Or the cancer that may come back in the future?

Rengan and other researchers at UW Medicine are pioneering a third way to cure cancer. It involves re-imagining how we use radiation and immunotherapy to achieve a lasting cure.

No Higher Calling
Rengan grew up with a father who was a nuclear chemist and a mother who was a biologist, so he understands the power of research and the potential of radiation to fuel scientific discovery. His parents inspired him to pursue an MD and PhD. But it was his patients who inspired him to become a radiation oncologist.

Repeatedly during his medical training, Rengan found that the most powerful patient interactions were at the bedside of cancer patients.

“It is a deep and sacred privilege to interact with somebody at an inflection point in their lives. To be a companion to somebody as they are navigating a pretty terrifying wilderness and to try and offer them some light — that’s the essence of what it means to be a doctor,” says Rengan.

A researcher and a practicing radiation oncologist, Rengan insists that he is a physician first. But his research is breaking new ground in the field of cancer care.

Fighting the Cancer You Can’t See
“One of the most significant advances in cancer care in the last decade has been the use of immunotherapies,” says Rengan. “The immune system is an incredible tool in the arsenal against cancer.”

In fact, the immune system is the only system in our body that has the power to destroy cells — including cancer cells. Immunotherapies allow the immune system to mount an unfettered attack against cancer. However, immunotherapies work less than half of the time in cancer patients and that’s because not everyone’s immune system recognizes cancer as a legitimate threat.

“The theory is that the immune system does not always recognize cancer as foreign,” says Rengan. “Remember cancer cells are made up of our own tissues. They are made up of our own DNA, only there are some errors in the DNA that didn’t get corrected. So, for the most part, cancer belongs to us. The immune system attacks anything that does not belong to us.”

If the immune system cannot recognize the cancer, most current FDA-approved immunotherapies don’t work. But what if you could train the immune system to better detect cancer?

Rengan and his team are breaking new ground using radiation as their weapon of choice to help the immune system better recognize the threat within.

Waves of the Future
When you use high-dose, high-intensity radiation to kill tumor cells, the cancer dies in a way that releases proteins or “neoantigens” that the immune system will recognize as foreign — thereby helping it to recognize cancer no matter where it’s located in the body, and with the help of immunotherapies, to eliminate it — potentially forever.

“Now the immune system knows what to look for because it has seen the footprint of these cancer cells. Because the immune system now recognizes the cancer, it can eradicate it throughout the body. We’re turning that tumor cell into a vaccine against itself,” says Rengan.

Historically, X-rays have been the primary type of radiation used to treat cancer. However, Rengan is discovering that neutron and proton radiation may be even more effective at uncloaking some types of cancer and, in some cases, cause fewer side effects and damage less surrounding tissue.

UW Medicine has the only department in the U.S. that has X-ray, proton and neutron radiation at its disposal, putting us in a unique position to explore the full potential of this treatment.

In collaboration with Fred Hutchinson Cancer Research Center, UW Medicine researchers have put together a family of clinical trials examining the optimal way to use radiation to trigger an immune response for a host of different cancers, including melanoma, renal cell carcinoma, lung cancer and prostate cancer among others.

Investigators have already had tremendous success using neutron radiation with immunotherapy to melt away cancer cells in patients with widespread, resistant Merkel cell carcinoma. Based upon these promising findings, the investigators now have an ongoing bladder cancer trial and plan to examine this approach in a broader spectrum of cancers.

“This is the future of radiation oncology,” says Rengan. “Not simply being a companion to the surgeon’s scalpel, but a whole different weapon that empowers the body to rid itself of the cancer it’s facing now and protect itself against cancer for future years to come.”

However, the future of radiation oncology depends heavily on the generosity of donors.

Donors Fuel This Work
The pipeline from an experiment in a petri dish to a verifiable treatment is a long one involving many steps, including clinical trials. As opposed to drug clinical trials, which are often well funded by drug companies with a stake in helping their drug reach the market, no one owns radiation, Rengan points out. So there is a big difference in how discoveries move through the pipeline.

With radiation clinical trials, there are many funding gaps to fill — making donors indispensable partners in our fight against cancer.

“In the field of radiation oncology, when we want to come up with novel ways to use radiation to improve the care of cancer patients, it must come through self-funded trials,” says Rengan. “We get some funding through the NIH, but there is a huge gap where donors play a vital role.”

For this reason, when a donor decides to support radiation oncology, whether they give a hundred dollars, one million dollars or more, they are making a meaningful impact in cancer care.

“We are relying on donors to help us define the future of cancer care,” says Rengan. “Donor funds are critical to shortening the timeline from leading-edge research conducted in the petri dish to cutting-edge therapies. Every donation makes a difference helping us translate basic research into improved clinical outcomes for our patients.”

Written by Eleanor Licata

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