Newswise — Ashish Shah, M.D., has assumed the newly created position of director of clinical trials and translational research and principal investigator in the Section of Virology and Immunotherapy at Sylvester Comprehensive Cancer Center’s Brain Tumor Initiative (BTI) at the University of Miami Miller School of Medicine. Dr. Shah, who calls himself a “quadruple ’Cane,” returns to the site of his undergraduate studies, medical school, and residency as a faculty member. This follows a year-long fellowship at the National Institutes of Health, where he focused on clinical trial design and translational neuro-oncology.

Now, Dr. Shah’s mission is to marry the clinical trials experience with his laboratory research and neurosurgery background to help the team bring novel therapeutics to patients with brain tumors.

Dr. Shah’s work will focus on the highly aggressive glioblastoma, which represents about half of all malignant brain tumors.

“We expect Dr. Shah to very quickly become one of the nation’s most recognized brain tumor researchers,” said Ricardo J. Komotar, M.D., director of the Sylvester BTI and professor of neurological surgery at the Miller School. “Dr. Shah is not only a world-class surgeon, but also does cutting-edge research. His role is to bring bench research to the clinic and bring clinical trials to our program.”

This coupling of neurosurgery expertise with a dynamic research focus is rare, and Dr. Shah joins Michael Ivan, M.D., BTI’s director of research, in fulfilling this dual role. Not only has Dr. Shah performed some of the most complex brain tumor surgeries, he has also published scores of papers on novel therapies and treatment approaches.

“You need to make sure that the laboratory and the operating room for your patients are well connected,” said Dr. Ivan. “There are only a handful of programs in the country that build a bridge from bench to bedside in brain cancer research. It means developing a brain tumor treatment in the laboratory that can make it to a clinical trial and be translation-tested for rapid application to patients.”

Ricardo J. Komotar, M.D., director of the Sylvester BTI and professor of neurological surgery at the Miller School

Improving Glioblastoma Outcomes

Most of Dr. Shah’s work will focus on the highly aggressive glioblastoma type of brain tumor, which represents about half of all malignant brain tumors. Although nearly all glioblastoma tumors recur following removal, thanks to innovative approaches taken at the BTI, patients here have some of the best outcomes in the country.

“I think the success of our world-class institute is largely due to a workflow we’ve implemented that allows us to maximize the amount of tumor we remove from the patients without compromising functionality,” Dr. Komotar said. “We do this through minimally invasive approaches like the laser thermal therapy, endoscopic approaches, fluorescence-guided surgery, and radiosurgery.”

He points to the laser interstitial thermal therapy, an ablative procedure, as one of the most promising techniques perfected here. This approach enables tumor cell killing through a 2 mm incision, while inducing the immune system to attack the tumor. The technique is lengthening remission by years in some patients, and Dr. Shah looks toward leading clinical trials for this therapy in 2023 to extend its applications.

Viral-based Gene Therapy

Much of Dr. Shah’s research focus, however, will focus on viruses associated with brain tumors, which he sees as fundamental to understanding glioblastoma in particular, and which may underlie curative treatment that has been so elusive in this complex cancer.

Viral-based gene therapy uses viruses to deliver genes into cancer cells and, by changing their fundamental genome, make them more susceptible to cancer treatments. Working with colleagues, Dr. Shah recently discovered a key role of endogenous retroviruses in glioblastoma development, and is also working to develop virotherapy that involves delivering tumor-selective “suicide genes,” using a novel retrovirus.

This viral-based gene therapy approach reprograms cancer cells to be sensitive to harmless “prodrugs,” eliciting a robust anti-tumor immune response. In clinical trials, it has been shown to extend overall survival by several months for certain high-grade gliomas.

“On the one hand, we’re trying to find out which viruses are causing the cancer, and on the other, we’re trying to use viruses to treat cancer,” he said.

Michael Ivan, M.D., BTI’s director of research

What’s Ahead

The team is planning future biomarker-driven virotherapy trials, as well as trials that will help predict which patients may benefit from certain therapies.

“The treatments we have to date have failed. Now we are working to harness the immune system to recognize these tumors and fight them off. Potentiating the immune response against our brain tumors is critical,” Dr. Shah said. “If we can use retroviruses to both kill tumors and induce an immune response, that is where I think the future is.”

Dr. Ivan, whose lab is adjacent to Dr. Shah’s, is enthusiastic about the new collaboration. “I think that we have developed a very comprehensive research program here, and we're excited to move forward,” he said. “We really felt recruiting Dr. Shah to this new position offers our patients additional access to new treatment and, ultimately, better outcomes.”

Dr. Komotar added, “One of the most exciting parts of my job is seeing the growth of our brain tumor program over the last several years, not only in terms of the number and the volume of brain tumors that we're taking care of, but also the world-class people we are surrounding ourselves with. Dr. Shah fits right into that. He was a top recruit this year.”