The quest for a new cancer treatment takes an important step

An anti-cancer therapy invented at Rice University has reached a milestone in clinical trials, a major development for decades to develop a treatment that destroys tumors without the debilitating side effects of chemotherapy, invasive surgery and radiotherapy.

Thirteen of the first 15 prostate cancer patients treated in a clinical trial of nanoparticle-based focal therapy showed no detectable signs of cancer one year after treatment, according to a study published this week in the Proceedings of the National Academy of Sciences (PNAS).

The paper presents results from 16 patients treated at the Icahn School of Medicine at Mount Sinai in New York. It would be the first published clinical study of a photothermal anticancer therapy – a therapy that uses bright nanoparticles to heat and destroy tumors – in a peer-reviewed scientific journal, the authors of the journal said. # 39; study.

In the study, 16 men aged 58 to 79 years with low-to-medium risk localized prostate cancer agreed to participate in a trial of AuroLase treatment, a focal ablation therapy which uses gold nanoparticles to heat and destroy tumors. Fifteen of the 16 patients underwent two-day treatment, received an intravenous infusion of nanoparticles on the first day, and underwent image-guided ablation treatment on the second day. All patients returned home on the day of treatment and returned for follow-up testing three months, six months, and one year after treatment. Of the 15 who completed treatment, only two showed detectable signs of cancer during follow-up biopsies and MRIs a year later.

"The infusion of nanochill gold and silica allows a targeted therapy that treats cancer while sparing the rest of the prostate, thereby preserving the patient's quality of life by reducing unwanted side effects, such as erectile dysfunction and / or urine leakage "Dr. Ardeshir Rastinehad, lead author of the study and lead investigator of the trial, associate professor of urology and radiology at the Icahn Medical School of Mount Sinai.

The trial, ongoing and that treated 44 patients at Mount Sinai and in two other clinical sites in Michigan and Texas, is the culmination of a 20-year quest led by Naomi Halas, an engineer. at Rice University and nanoscientist, and bioengineer Jennifer West of Duke University. Halas and West, co-authors of the new study, first envisioned nanoparticle-based therapy around the year 2000 while working together at Rice's Brown School of Engineering. .

Particles, tiny spheres of silica with a thin outer layer of gold, are called nanoshells. They are about 50 times smaller than a red blood cell and Halas invented them at Rice in 1997. By varying the thickness of the shell to gold, Halas showed that she could tune into nanococci to interact with specific light wavelengths. Around 2000, she and West invented a method of destroying cancer cells by heating nanocells with a low-power near-infrared laser, able to cross healthy tissue safely.

The work has been rewarded with national awards and the press. In the early 2000s, Halas and West co-founded a Houston-based start-up, Nanospectra Biosciences, to develop the technology for clinical purposes.

Around that time, Halas's father, then aged 85, was diagnosed with prostate cancer.

"He had profound hearing loss and was legally blind, so I had to be the communication link between him and his urologist," said Halas. "I know a lot about prostate cancer in people because of my dad."

Halas stated that she would never forget when her father asked her if her invention could be the solution to her prostate cancer.

"He knew about nanococci," she said. "The story was published in Business Week and he posted the cut on a wall in his office."

At the time, Nanospectra was still conducting the preclinical work needed to show that nanoshells could be used safely in humans.

Two years after her radiation therapy, it was almost impossible for her to urinate.

"It was terrible," Halas remembered. "He came and went to the hospital every week, the doctor would put a catheter in. He would come home, things would be fine for a few days, then he would have to go to the emergency room. Was amazing what he went through. "

She remembers very well a conversation that always motivates her.

He said, "If you could stop one person from going through the hell I lived, it would be worth it," said Halas.

From the beginning, West and Halas had devised a treatment that would destroy cancer without the debilitating side effects often associated with chemotherapy, invasive surgery and radiation therapy. And this had been proven in their early studies of cell cultures and mice.

"Science has not changed," said West. "If you go back to our original PNAS paper, where we did the first studies on animals, there is nothing fundamentally different in science. "

But getting clinical trials approved by the Food and Drug Administration was not easy, partly because the technology was revolutionary.

"We were the first truly designed nanoparticle to enter humans," said West. "At first, the FDA was not sure how to handle this type of material.We had something that looked like an injectable liquid in an IV bag." It was a drug or of a device? There was a time when the FDA was discussing the creation of a brand new division just for nano ".

In the end, the agency chose to regulate the treatment, which Nanospectra dubbed AuroLase Therapy, as a medical device. Safety-focused clinical trials began almost 10 years ago with a study of advanced head and neck cancer. Halas said Nanospectra had learned valuable lessons at every step, but that was another big step forward – that of medical imaging – that paved the way for the success of prostate cancer.

In 2011, researchers at the National Institutes of Health released the results of a new technique combining ultrasound imaging and MRI to resolve prostate tumors with millimeter precision, Halas said. Clinicians have begun to adopt the technique of "fusion biopsies", a procedure for targeting needle biopsies at the site-specific suspected tumors.

Rastinehad, one of the leading researchers working on the development of fusion biopsy, joined Mount Sinai in 2015 and was one of the first proponents of the use of the platform. fusion imaging for "focal therapy", a minimally invasive treatment to target tumors without the risk of incontinence and impotence associated with treatments of the entire gland, such as surgical removal of the prostate or radiation.

For Halas and West, the new published study is another milestone in a 20-year journey that has always been personal and deeply moving.

"Tropical storm Allison hit while we were conducting our first animal experiments at the Texas Medical Center," recalls West. "Many of the MRI instruments at animal research centers were destroyed and we finally had to run MRIs on our mice in the same facilities that were used to image the patients." It was deeply moving to see the impact of cancer on humans, wait there with them and think that what we were developing might someday, hopefully, really help them. "

Halas' father died several years ago, but she said that she thought of him every day.

"There is a bigger picture here," she said. "This (study) has 16 men, but when will it reach 16,000? Sixteen million? Because one in nine men will have to deal with this in their lifetime. The idea that this treatment could alleviate the side effects, and the misery that my father experienced is really heartwarming. "

West said the results show what is possible when doctors and engineers work together to solve problems.

"This work demonstrates the power of collaboration between engineering and medicine," she said. "It shows how collaboration can translate exciting new technologies into clinical medicine to improve the lives of patients."