In association with its 50th anniversary, the American Society of Clinical Oncology (ASCO) has named Daniel D. Von Hoff, M.D., FACP, one of ASCO’s 50 Oncology Luminaries, celebrating 50 doctors who over the past half-century have significantly advanced cancer care.
Dr. Von Hoff is Chief Scientific Officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials and Physician-In-Chief and Distinguished Professor at Phoenix-based Translational Genomics Research Institute (TGen). He is an internationally recognized physician and scientist whose research during the past 30 years has contributed to the development of many anticancer agents that are routinely used in clinical practice. Among these drugs are fludarabine, mitoxantrone, paclitaxel, docetaxel, irinotecan, topotecan, nelarabine, gemcitabine, vismodegib, and nanoparticle paclitaxel.
ASCO was founded in 1964 by oncologists to improve the care of cancer patients. Profiles of the 50 Oncology Luminaries are being featured on the ASCO website, and their accomplishments will be celebrated at ASCO’s 50th annual meeting, May 30-June 3 in Chicago.
Although it is difficult to pick one highlight of his career, Dr. Von Hoff and his team played an instrumental role in the development of gemcitabine, the first drug to improve the survival of patients with stage IV pancreatic cancer. In 1997, they published the results of a clinical trial that showed that gemcitabine not only increased the rate of clinical benefit in patients with pancreatic cancer compared with fluorouracil (5-FU), but it also improved overall survival.
This work was followed by recognition of the activity of nab-paclitaxel plus gemcitabine against pancreatic cancer with the recent finding that that regimen also improved survival for patients with stage IV pancreatic cancer. On Sept. 6, 2013, the U.S. Food and Drug Administration (FDA) approved nab-paclitaxel as a frontline therapy for patients with advanced pancreatic cancer.
International clinical trials that led to the FDA’s approval were led by Dr. Von Hoff at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership of Scottsdale Healthcare and TGen, at Scottsdale Healthcare Shea Medical Center in Scottsdale, Ariz.
Dr. Von Hoff has also been instrumental in the concept of development of personalized therapy for patients with refractory cancer based on using molecular techniques to profile their cancers. This work included the initial clinical trials to determine what percentage of patients could benefit from that approach.
Dr. Von Hoff has spent the past 30 years of his career leading teams in phase I trials and the development of new therapies, first as the founding director of the Institute for Drug Development at the Cancer Therapy and Research Center in San Antonio, then as the director of the Cancer Center and Professor of Medicine at the University of Arizona. He also is Professor of Medicine at the Mayo Clinic and serves as Chief Scientific Officer for US Oncology.
When Dr. Von Hoff was awarded ASCO’s David A. Karnofsky Memorial Award in 2010, he took several minutes at the beginning of his lecture to memorialize all of the patients that he and his team had lost during phase I trials the previous year, mentioning several of them by name. The gesture reflected what Dr. Von Hoff named as the greatest accomplishment of his career: working hard to help as many people as he could.
“I have been extremely fortunate to have many great (and incredibly patient) teachers, mentors, and co-workers,” Dr. Von Hoff said. “Truly though I think the greatest teachers and mentors for me have been those I have been privileged to care for.”
Researchers have discovered why multiple myeloma, a difficult to cure cancer of the bone marrow, frequently recurs after an initially effective treatment that can keep the disease at bay for up to several years.
Working in collaboration with colleagues at Princess Margaret Hospital in Toronto, researchers from Mayo Clinic in Arizona and the Translational Genomics Research Institute (TGen) in Phoenix were part of the team that conducted the study published in the Sept. 9 issue of Cancer Cell.
The research team initially analyzed 7,500 genes in multiple myeloma cells to identify genes which when suppressed made cancer cells resistant to a common class of drugs called proteasome inhibitors such as bortezomib or carfilzomib. Then, the team studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that control response to the proteasome inhibitor and the mechanism underlying the drug resistance that is the barrier to cure.
The findings showed recurrence was due to an intrinsic resistance found in immature tumor progenitor (mother) cells is the root cause of the disease and also spawns relapse. The research demonstrates that although the visible cancer cells that make up most of the tumor are sensitive to the proteasome inhibitor drug, the underlying progenitor cells are untouched by this therapy. These progenitor cells then proliferate and mature to reboot the disease process, even in patients who appeared to be in complete remission.
“Our findings reveal a way forward toward a cure for multiple myeloma, which involves targeting both the progenitor cells and the plasma cells at the same time,” says Rodger Tiedemann, M.D., a hematologist specializing in multiple myeloma and lymphoma at Princess Margaret. “Now that we know that progenitor cells persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this residual disease in patients, and attempt to target it with new drugs or with drugs that may already exist.”
“Some myeloma cells are too immature to be caught by the drugs and thus hide underground only to reemerge later,” says Keith Stewart, M.B., Ch.B., Dean for Research at Mayo Clinic in Arizona and contributor to the study. “This study has wide implications in the search for a cure of this common blood cancer as this ‘progenitor cell’ will have to be targeted.”
Jonathan Keats, Ph.D., head of TGen’s Multiple Myeloma Research Laboratory, said: “This study, which leverages data generated at TGen as part of the Multiple Myeloma Genomics Initiative, shows how mutations acquired by multiple myeloma tumors can make a tumor resistant to specific therapies and highlights the importance of TGen’s precision medicine approaches.”
Dr. Tiedemann says: “If you think of multiple myeloma as a weed, then proteasome inhibitors are like a goat that eats the mature foliage above ground, producing a remission, but doesn’t eat the roots, so that one day the weed returns.”
The study — Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma — was funded by the National Cancer Institute, Multiple Myeloma Research Foundation, Leukemla and Lymphoma Society and Canadian Cancer Society, the Arthur Macaulay Cushing Estate and The Princess Margaret Cancer Foundation.
Dr. Tiedemann is the Molly and David Bloom Chair in Multiple Myeloma Research, at the University of Toronto, Dr. Stewart is the Anna Maria and Vasek Pollack Professor of Cancer Research at Mayo Clinic. Dr. Keats is an Assistant Professor in TGen’s Integrated Cancer Genomics Division.
Kathleen H. Goeppinger, Ph.D., President and Chief Executive Officer, Midwestern University, announced the appointment of Jeffrey M. Pearl, M.D., as Program Director and Professor for the College of Health Sciences’ Physician Assistant Program.
Dr. Pearl comes to Midwestern with a distinguished academic career with a commitment to research and education. He served as a Pediatric Cardiothoracic Surgeon for Phoenix Children’s Hospital and specializes in congenital heart surgery and transplantation. Dr. Pearl is also a Professor of Surgery at Mayo Clinic and a Clinical Professor for the University of Arizona College of Medicine Phoenix. He earned his B.A. from the University of California, Berkeley, and his M.D. from the University of California, Los Angeles Medical School.
Jennifer Linder, M.D. – Chief scientific officer, PCA Skin
Linder, a board-certified dermatologist and a fellowship-trained Mohs micrographic skin surgeon, guides all product development and clinical trials for PCA Skin, ThinkGlobal’s 2013 Exporter of the Year in the Health & Beauty category. She is one of the foremost U.S. experts in the use of the cosmetic filler, Sculptra, and is also on medical advisory boards for Botox and Juvéderm.
Surprising fact: “While I majored in engineering in college, I pursued my love of art through painting classes. Through medical school and into my life today, I still paint.”
Biggest challenge: “My husband and I spent five years living in separate cities – before and after marriage. Being apart was difficult, but we traveled to visit each other frequently.”
Fifty Most Influential Women in Arizona Business – Every year in its July/August issue Arizona Business Magazine features 50 women who make an impact on Arizona business. To see the full list, read the digital issue >>
The Side-Out Foundation’s breast cancer pilot study, led by the Translational Genomics Research Institute (TGen), Translational Drug Development (TD2) and Scottsdale Healthcare, has shown that cancer patients do better when their treatment is guided by molecular profiling.
Specifically, 52 percent of patients with advanced breast cancer received clinical benefit – meaning their disease was controlled for a longer time – when their cancer was treated based on addressing the abnormal proteins in their tumor, according to the study conducted at the Virginia G. Piper Cancer Center Clinical Trials, a partnership of Scottsdale Healthcare and TGen.
Each patient’s treatment was “personalized,” meaning that the therapy they received was based on their individual tumor biology.
“This study demonstrates the feasibility of personalized cancer treatment, and shows that this approach merits further investigation in future studies,” said Gayle Jameson, Nurse Practitioner at Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials and the study’s Principal Investigator.
“The success of this pilot study will lead to a larger study and hopefully greater clinical benefit for more patients with advanced breast cancer,” said Jameson, who presented the results of the study in June at the 2013 American Society of Clinical Oncology (ASCO) in Chicago.
Due to the overwhelmingly positive results, a new study incorporating additional technology for tumor analysis, Side-Out II, will open at the Virginia G. Piper Cancer Center Clinical Trials in the near future for patients with advanced breast cancer.
“The success of our pilot proof-of-concept study has established a firm launching pad for the upcoming Side-Out II study, which involves a more in-depth investigation of tumor biology with an expanded repertoire of tests to direct personalized treatment,” said Dr. Jasgit Sachdev, M.D., a breast cancer specialist and Associate Professor at the Virginia G. Piper Cancer Center Clinical Trials.
“By showing the significant advantages of molecular profiling, this pilot study has enabled us to move forward with a project that should strengthen the evidence for using this approach in routine clinical care.”
The recent pilot study built on previous studies by Scottsdale Healthcare and TGen that showed the value of guiding treatment based on molecular profiling, in which each patient’s tumor was analyzed for protein abnormalities that may “drive” the cancer’s growth. The results pointed investigators toward specific genetic changes that might be addressed by specific medications.
Beyond molecular profiling, the pilot study also included mapping proteomic pathways within the tumor tissue so each patient could receive a highly targeted regimen designed to impede their cancer growth.
All of the patients in the recent study had advanced breast cancer that had progressed following multiple previous chemotherapy treatments. Of the 25 patients, 13 received clinical benefit as a result of molecular profiling. For all 25 patients, the therapy selected based on their tumor analysis was different than what they would have received in their next planned treatment, if they had not participated in the study.
The Virginia G. Piper Cancer Center at Scottsdale Healthcare was the lead site in the 2-½ year pilot study. In addition, patients in the study were treated at Virginia Cancer Specialists, US Oncology, in Fairfax, Vir.; and at Evergreen Hematology & Oncology in Spokane, Wash.
Translational Drug Development (TD2), a TGen company, managed the pilot clinical trial, and will also oversee the follow-on study, Side-Out II.
“This was an exciting study for TD2,” said Linda Vocila, BSN, RN, Director of Clinical Operations at TD2 and co-author of the study. “It demonstrates that close collaboration between physicians and scientists leads to greater clinical benefit for patients with cancer.”
Two labs analyzed tissue: the Center for Applied Proteomics and Molecular Medicine (CAPMM) at George Mason University in Manassas, Vir.; and Caris Life Sciences in Phoenix.
The Side-Out Foundation of Fairfax, Vir., sponsored the study.
To participate in a clinical trial at the Virginia G. Piper Cancer Center, please contact Patient Care Coordinator Joyce Schaffer at 480-323-1339 or firstname.lastname@example.org.