New Clinical Trial for Early-Stage Eye Melanoma Offers Study of Targeted Therapy

Credit: Photo courtesy: Roger Barone / Wills Eye Hospital.

Wills Eye Hospital's Carol Shields, MD examines patient (clinical study participant). Oncology research fellow, wearing protective eyewear, also observes. 

Newswise, April 3, 2017 – A first-of-its-kind, potentially groundbreaking new option for treating a form of eye cancer is now in its first phase-1 clinical research trial at Wills Eye Hospital in Philadelphia.

The treatment, called light-activated AU-011, developed by Aura Biosciences of Cambridge, Massachusetts, is an investigational drug that targets and aims to selectively destroy malignant cancer cells in patients who have life-and vision-threatening eye cancer, also known as, ocular melanoma.

Ocular melanoma is a malignant cancer that develops within the eye. It affects as many as 3,000 people per year in the United States. While melanoma is often associated with skin cancer from sun exposure, ocular melanoma does not relate to the sun, developing instead from abnormal pigmented cells in the eye.

The danger with ocular melanoma is that there are often no symptoms, making it difficult to detect resulting in the potential of quietly spreading throughout other parts of the body.

Risk factors include being Caucasian, fair-skinned, and the risk of developing the disease also increases as we age. The best way to detect ocular melanoma is to have an annual comprehensive dilated eye exam by a board certified ophthalmologist.

This innovative treatment approach now being investigated at Wills Eye Hospital uses viral nanoparticle conjugates, which is a targeted therapy of growing interest in medicine.

The treatment involves injecting the AU-011 investigational drug into the eye affected by cancer followed by the brief use of a companion ophthalmic laser treatment to activate the drug.

The investigational drug is expected to destroy the membranes of the ocular melanoma while sparing key eye structures which may allow for the potential of preserving patients’ vision.

“Patients with ocular melanoma currently have few treatment options available that can effectively destroy tumor cells while preserving vision. Conducting valuable research trials like this one enables clinicians and researchers to examine new and better options for patients throughout the world,” said, Carol L. Shields, MD, Co-Director of the Ocular Oncology Service at Wills Eye Hospital where the first US patient was treated.

Dr. Shields is also a key investigator in the research trial and the author of numerous top peer-reviewed publications on ocular melanoma, including identification of the risk factors for early diagnosis (Kaliki & Shields 2016 in Nature Eye.)

Currently, the primary treatment option for ocular melanoma is plaque radiotherapy which was, in part, pioneered in the United States by the Shields Oncology team at Wills Eye Hospital.

While that therapy has achieved high success throughout the years in tumor control for patients, this new potential targeted therapy may open the door to a less invasive method of treatment.

“We are delighted to be one of the pre-eminent clinical trial sites in the nation for this unique and promising treatment. Wills Eye has always been a leader in the clinical application of emerging new therapies. We are 100% behind our world’s best oncology team,” said, Julia A. Haller, MD, Ophthalmologist-in-Chief, Wills Eye Hospital.

The trial, which began in early 2017, is expected to enroll up to 12 patients at Wills Eye and other clinical trial sites.

Trial investigators will focus on evaluating the safety of two dose levels of AU-011 for the treatment of patients with small to medium primary ocular melanoma. Potential participants must have a confirmed ocular melanoma diagnosis not previously treated. Patients treated in the trial will be observed and followed for 2 years.

About Carol L. Shields, MD: Dr. Carol Shields is Co-Director of the Oncology Service, Wills Eye Hospital, and Professor of Ophthalmology at Thomas Jefferson University in Philadelphia. She has authored or co-authored 9 textbooks, over 1000 articles in major journals, nearly 300 textbook chapters, given over 600 lectureships, and has received numerous professional awards of major national and international standing including The American Academy of Ophthalmology Life Achievement Honor Award.

Dr. Carol Shields is a member of numerous ocular oncology, pathology and retina societies and has delivered 30 named lectureships in America and abroad. She practices ocular oncology on a full time basis with her husband, Dr. Jerry Shields on the Oncology Service at Wills Eye Hospital.

About Wills Eye Hospital: Wills Eye Hospital is a global leader in ophthalmology, established in 1832 as the nation’s first hospital specializing in eye care. U.S. News & World Report consistently ranks Wills Eye as one of America’s top ophthalmology centers since the survey began and has the most nationally ranked ophthalmologists in the country.

Wills Eye is a premier training site for all levels of medical education. Its resident and post-graduate training programs are among the most competitive in the country. One of the core strengths of Wills is the close connection between innovative research and advanced patient care. Wills provides the full range of primary and subspecialty eye care for improving and preserving sight, including cataract, cornea, retina, emergency care, glaucoma, neuro-ophthalmology, ocular oncology, oculoplastics, pathology, pediatric ophthalmology and ocular genetics, and refractive surgery.

Ocular Services include the Wills Laser Correction Center, Low Vision Service, and Diagnostic Center. Its 24/7 Emergency Service is the only one of its kind in the region. Wills Eye also has a network of nine multi-specialty, ambulatory surgery centers throughout the tri-state area. To learn more, please visit www.willseye.org

A Beach Lover’s Dream: A Step Toward Long-Lasting Sunscreen

Newswise, April 3, 2017 — In a perfect world, people would diligently reapply suncreen every couple of hours to protect their delicate skin from damaging solar radiation. But in reality, few people actually adhere to reapplication guidelines, and those who do hardly relish the task.

To develop longer-lasting sunscreens, researchers are trying to answer a basic question: How do sunblock ingredients work?

The researchers presented their work at the 253rd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 14,000 presentations on a wide range of science topics.

“Sunscreens have been around for decades, so you’d think we know all there is to know about them — but we really don’t,” Vasilios Stavros, Ph.D., says.

 “If we better understand how the molecules in sunscreen absorb light, then we can manipulate the molecules to absorb more energy, and we can protect the molecules from degradation. If the molecule doesn’t break down, there's no need to reapply.”

A typical sunscreen sold at a drug store contains many different ingredients, Stavros explains.

 “We wanted to break these lotions and creams down like a jigsaw puzzle — take one of the ingredients and understand it from a molecular point of view without interactions from the other component parts.”

The researchers, who are at the University of Warwick (U.K.), started by focusing on sunscreen ingredients called chemical filters, which are molecules that absorb UV light. They have studied about 10 common chemical filters so far.

When these molecules absorb energy from the sun, Stavros explains, they enter into an excited electronic state. Other molecules are likely to break under the sun's glare, sometimes releasing dangerous free radicals. But instead of breaking, chemical filters can shimmy and shake themselves back into the more stable ground state, releasing energy as harmless heat. The problem is that these chemical filters can fail, breaking into pieces or getting stuck in the excited state.

To figure out how to prevent chemical filter dysfunction, Stavros’ team used lasers to simulate the sun’s energy and to monitor the flow of energy through the chemical filters as the molecules traverse from the ground state to the excited state and back again (or not).

For example, the researchers found that about 10 percent of the molecules of the sunscreen ingredient oxybenzone get locked in an excited state when the laser is shone on them.

 “When that chemical filter is in an excited state, its atoms are rotating around certain bonds,” Stavros says. “If we can manipulate this rotation by adding different chemical groups, we could help the molecule find its way back to the ground state,” he says, noting that they plan to work on this project soon.

In addition, the researchers are beginning to study the filters in a context that is more similar to an actual sunscreen, rather than in isolation. “We are increasing molecular complexity, building the jigsaw puzzle,” Stavros says.

He adds that analyzing the data has been a challenge, but one that the team is tackling head-on. In the end, the data analyses and chemical manipulations should shed more light on how sunscreens protect against sun damage so researchers can develop longer-lasting concoctions.

Stavros acknowledges funding from the Engineering and Physical Sciences Research Council, the Royal Society, The Leverhulme Trust and the University of Warwick (all in U.K.).

The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With nearly 157,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

‘Sniffing’ Urine to Detect Prostate Cancer Could Prevent Unnecessary Biopsies

Newswise, April 3, 2017— On the list of dreaded medical tests, a prostate biopsy probably ranks fairly high. The common procedure requires sticking a needle into the prostate gland to remove tissue for assessment.

Thousands of men who undergo the uncomfortable procedure, prompted by a positive PSA (prostate-specific antigen) test, ultimately don’t require cancer treatment. Today, scientists report progress toward minimizing unnecessary biopsies: They have identified the molecules likely responsible for the scent of prostate cancer, which could be detected by chemically “sniffing” urine.

The researchers will present their results at the 253rd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 14,000 presentations on a wide range of science topics.

“The idea for this project started with a study published in 2014 showing that trained canines could detect prostate cancer with greater than 97 percent accuracy,” says Mangilal Agarwal, Ph.D., the project’s principal investigator.

His team had already been working on a sensor to sniff hypoglycemia on a person’s breath as dogs have also been shown to do. When the prostate cancer study appeared in the Journal of Urology, Agarwal’s lab set out to determine what molecules the dogs might be sensing.

“If dogs can smell prostate cancer, we should be able to, too,” says Amanda Siegel, Ph.D., who is presenting the work at the meeting. Both Agarwal and Siegel are at the Integrated Nanosystems Development Institute of Indiana University-Purdue University Indianapolis (IUPUI) and the Richard L. Roudebush VA Medical Center.

Prostate cancer is the third most common type of cancer in the United States. In 2016, more than 180,000 new cases were diagnosed, according to the U.S. National Institutes of Health’s National Cancer Institute.

Early detection has been critical to saving the lives of many men with prostate cancer. But diagnosing the disease can be fraught with challenges.

The screening test that doctors use now to determine whether to perform a biopsy assesses PSA levels in a blood sample. The prostate gland normally produces this protein in small amounts. Increased levels, however, can indicate many different conditions besides cancer, including prostate infection. As a result, the test is widely recognized as flawed and often leads to unnecessary biopsies.

“Currently, about 60 percent of men who get a biopsy to test for prostate cancer don’t need to get one,” Siegel says. “We hope our research will help doctors and patients make better-informed decisions about whether to have a biopsy, and to avoid unwarranted procedures.”

To determine which molecules wafting from urine could indicate prostate cancer in a patient, the IUPUI and VA team collected urine samples from 100 men undergoing prostate biopsies.

To avoid issues that similar studies have had with sample degradation, Agarwal’s team developed a pre-processing step — adding sodium chloride and neutralizing the pH — to ensure the samples would remain intact during the analysis.

Then, they used gas chromatography-mass spectrometry to identify the volatile organic compounds floating in the “headspace” above the urine samples.

With this method, the researchers pinpointed a small set of molecules that showed up in 90 percent of the samples from patients with prostate cancer but not in samples from those who did not have the disease.

Next, the team plans to conduct large-scale tests at multiple health centers to validate their findings. They have also submitted a proposal for funding to confirm the molecular signature they identified by collaborating with a local dog trainer and comparing their technique’s results to those obtained with a canine nose.

Depending on the outcome of these projects, Siegel and Agarwal say their test could become available to patients and doctors within the next few years. In the short-term, urine samples would have to be sent to a lab for analysis, but the researchers say their ultimate goal is to design a sensor that can yield results in a doctor’s office.

The researchers acknowledge support and funding from the Richard L. Roudebush VA Medical Center.

The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With nearly 157,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences.

ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.