TGen-UCSF Study Published in Neuro-Oncology Provides Comprehensive Look at Brain Cancer Treatments

New clinical trial at UCSF, based on TGen genomic research, uses multiple drugs to cross blood-brain barrier and attack glioblastoma tumors

Led by the Translational Genomics Research Institute (TGen) and UC San Francisco (UCSF), a comprehensive genetic review of treatment strategies for glioblastoma brain tumors was published May 1 in the Oxford University Press journal Neuro-Oncology.

The study, Towards Precision Medicine in Glioblastoma: The Promise and The Challenges, covers how these highly invasive and almost-always-deadly brain cancers may be treated, reviews the continuing challenges faced by researchers and clinicians, and presents the hope for better treatments by harnessing the power of the human genome.

The study also describes a pioneering clinical trial underway for 15 patients at UCSF, guided by TGen research, in which an individual patient’s genomic profile is used to offer treatment recommendations to an expert, multidisciplinary panel.

“This study thoroughly explores how we arrived at the current standard-of-care, and how — through cutting-edge genomic technologies — we might find better answers for these patients who need our help today,” said Dr. Jeffrey Trent, TGen President and Research Director and the study’s senior author.

Funded by The Ben & Catherine Ivy Foundation, the study is one of several simultaneous and coordinated efforts seeking to uncover the molecular source of this deadly brain cancer with the goal of prolonging survival of glioblastoma patients.

“Despite pivotal advances in the characterization of genomic mutation in glioblastoma, targeted drug agents have so far shown minimal effect in clinical trials, and patient survival remains poor,” said Dr. Michael D. Prados, the Charles B. Wilson, MD, Endowed Chair in Neurological Surgery at UCSF, and one of the study’s co-lead authors.

One of the major difficulties in treating brain tumors is finding drugs that can penetrate the blood-brain barrier, which buffers the brain from the rest of the body’s blood-circulatory system. Located along capillaries, the blood-brain barrier protects the brain from rapid changes in the body’s metabolic conditions and minimizes exposure to molecules that are toxic to neurons in the brain.

“This study outlines strategies for overcoming past failures, primarily by applying targeted combination therapies that match the tumors’ genetic changes with drug compounds that can reach the central nervous system,” said Dr. Sara Byron, Research Assistant Professor in TGen’s Center for Translational Innovation, and the study’s other co-lead author.

Another major challenge in treating glioblastoma is its intrusive penetration into adjoining tissues, which prevents the complete surgical removal of the tumors from the brain, even with follow-up radiation and chemotherapy: “It is this invasive, infiltrative disease component that is the ultimate cause of recurrence, resistance and death,” the study says.

“All patients will continue to show tumor growth and progression because of rapidly proliferating infiltrative disease remaining after surgery,” according to the study. “Effective treatment for glioblastoma remains an unmet need.”

The only FDA-approved drugs to treat glioblastoma are temozolomide, nitrosoureas, and bevacizumab.

In the clinical trial begun at UCSF, multiple biopsies are performed on each patient at the time of surgery in different regions of the brain tumor. That is followed by extensive genome-wide profiling, leading to a selection of drugs that would target the brain cancer and diffuse regions of the lesion that cannot be removed by surgery.

Drug selection is individualized, and multiple FDA-approved agents (up to four) allowed. “Rules” for drug selection are implemented, using the specialized drug pharmacopeia designed for this trial. The drugs are chosen carefully, considered with knowledge about the ability of the drug to reach the brain and the patient’s past treatment history and concomitant therapies, with the assistance of multi-specialty, multi-institutional molecular tumor board that drafts a report to the treating physician.

In addition, “Small, informative, tissue-based clinical trials that take into account the individual molecular features of patients and provide early ‘go’ or ‘no go’ decisions are needed and should be prioritized over unselected, large, population-based strategies,” the study recommends.

A separate clinical trial that follows this path, also guided by TGen genomic research, is underway at Barrow Neurological Institute. This clinical trial also is funded by The Ben & Catherine Ivy Foundation. For more about this clinical trial, go to: www.tgen.org/home/news and click on March 10, 2015.

“These studies, and their associated clinical trials, have the potential to lift our knowledge of glioblastoma to an unprecedented new level,” said Catherine Ivy, President of The Ben & Catherine Ivy Foundation. “Developing drug compounds that breach the blood-brain barrier and are effective against tumors would fulfill one of the medical community’s most critical unmet needs, and boost the hopes of brain tumor patients everywhere.”

Contributing to the study published today were all three TGen Deputy Directors:  Dr. John Carpten, Deputy Director of Basic Science; Dr. Michael Berens, Deputy Director for Research Resources; and Dr. David Craig, Deputy Director of Bioinformatics.

TGen’s and HonorHealth’s Dr. Daniel Von Hoff Receives Top Honor from the Arizona Medical Association

Wallace A. Reed, M.D. Award recognizes innovative cancer treatments

Dr. Daniel D. Von Hoff, Distinguished Professor and Physician-In-Chief of the Translational Genomics Research Institute (TGen), will receive one of the top awards May 29 from the Arizona Medical Association (ArMA).

Dr. Von Hoff will receive the 2015 Wallace A. Reed, M.D. Award, recognizing his accomplishments in advancing innovative cancer treatments, said Dr. Nathan Laufer, President-Elect of ArMA.

“ArMA extends it wholehearted congratulations to Dr. Daniel D. Von Hoff for his many innovative contributions to the advancement of cancer care, especially in the realm of pancreatic cancer, one of the most difficult to treat of all cancer types,” Dr. Laufer said.

Dr. Von Hoff’s award will be presented at the 2015 ArMA President’s Award Banquet Dinner, 7-9 p.m. May 29 at the Phoenix Country Club, 2901 N. Seventh Street. The President’s Awards Banquet is held on Friday evening of each ArMA Annual Meeting, and honors the work of physicians, community members and organizations improving health care in Arizona.

“It is a profound honor to receive this award from my fellow physicians from across Arizona,” said Dr. Von Hoff, who also is Professor of Medicine at the Mayo Clinic, and Clinical Professor of Medicine at the University of Arizona.

“We must continue to strive to provide the very best care for our patients. To do that, we must constantly make new discoveries to create new and innovative treatments to better their lives,” said Dr. Von Hoff, who also is Chief Scientific Officer at US Oncology and at the Virginia G. Piper Cancer Center Clinical Trials at HonorHealth, formerly Scottsdale Healthcare, where TGen research discoveries are translated into new treatments for patients.

The Wallace A. Reed, MD Award recognizes innovation in health care by an individual or organization. It is named for the late Phoenix anesthesiologist, Dr. Wallace A. Reed, who more than four decades ago co-founded Phoenix Surgicenter, ushering in the era of outpatient surgical centers. The concept has been replicated nationwide, with more than 5,000 ambulatory surgery centers performing more than 22 million procedures each year. Dr. Reed passed away in 2014 at age 97.

The Arizona Medical Association (ArMA) is a voluntary membership organization for all Arizona medical and osteopathic physicians. It provides members with legislative advocacy, professional leadership, and 120 years worth of building community relationships.

ArMA’s mission is to promote and provide leadership in the art and science of medicine; to preserve and improve the health of all Arizonans; to represent Arizona physicians in the public forum; and to defend Arizona physicians’ freedom and ability to practice medicine in the best interests of their patients.