When primary tumors spread, or become metastatic — establishing beachheads on different organs in the body such as the liver, bone marrow, lung or brain — the outlook for a cancer patient turns grim.
Fred Hutchinson Cancer Research Center bioengineer and cancer researcher Dr. Cyrus Ghajar has focused much of his work on what causes breast cancer cells to metastasize. Now, with the help of a new $1 million grant from the W.M. Keck Foundation, Ghajar and his team are hoping to crack open a mystery that has long puzzled scientists in the field: Why do metastatic cells, which can proliferate in many organs, nearly always fail to grow in skeletal muscles, which account for as much as half the body mass of an adult?
“The lung is ‘fertile soil’ for breast cancer, as is bone marrow,” Ghajar said. “Nearly 90 percent of metastatic prostate cancer goes to the bone. But metastatic cells can sit within skeletal muscle for years, over decades, and almost never wake up.” Something unique in the microenvironment — the protein-rich milieu surrounding the cells of every organ and tissue — may be suppressing tumor growth in skeletal muscles. Ghajar is determined to find out what it is.
The Keck Foundation grant makes it possible for Ghajar and his team to carry out a series of complex experiments over three years aimed at pinpointing the factors or conditions that prevent metastatic cells from growing in skeletal muscles. They also will study whether it is possible to recreate that protective environment in more vulnerable organs, such as bone marrow or lungs, making them less hospitable to spreading cancer cells. The focus of their work will be on metastatic breast and prostate cancer.
Joining Ghajar in that effort are Fred Hutch prostate cancer researcher Dr. Peter Nelson, holder of the Endowed Chair for Prostate Cancer Research; functional genomics expert Dr. Patrick Paddison; developmental biologist Dr. Slobodan Beronja; muscle-biology expert Dr. Stephen Tapscott; and Dr. Kirk Hansen, a University of Colorado, Denver proteomics pioneer.
Ghajar, who is collaborating with Hansen on a number of projects, said that the Colorado researcher is renowned in the field for developing methods to not only identify proteins in cellular microenvironments, but also to determine ratios of components — how much one type of protein appears in the mix compared to others.
One arm of the project will involve identifying “metastasis suppressors” in the skeletal-muscle microenvironment. Protection could be provided by a particular protein, metabolite, mix of proteins or by a lack of specific molecules common in other tissue environments.
A second arm will use sophisticated laboratory techniques to pick apart the molecular components of very rare tumor cells that are known to take root in this hostile skeletal muscle environment.
Equipped with the findings from these two very different views of metastatic resistance, the team then plans to test whether they can manipulate those mechanisms to protect other tissues from metastasis without affecting normal health and function.
“This has the potential to be something big,” Ghajar said. “We are so excited by this question that we were stringing together funds to try and get this project going. Now, with funding like this, we have the time and money to do it right. It is amazing that the Keck Foundation is giving us a shot at this.”
— Sabin Russell / Fred Hutch News Service
On Monday, Aug. 21, Fred Hutchinson Cancer Research Cener pancreatic cancer physician-scientist Dr. Sunil Hingorani was presented with the newly created Raisbeck Endowed Chair for Pancreatic Research, established by Fred Hutch donors James and Sherry Raisbeck.
Faculty and staff, donors, and family celebrated Hingorani and the Raisbecks at a reception in a room decked out in purple, the color associated with pancreatic cancer.
“Thank you for this honor,” Hingorani said to the Raisbecks and the several dozen guests gathered just down the hall from the lab where his team is working to develop cures for this notoriously deadly cancer. “I’ll try to continue to do what I can to deserve it.”
Hingorani’s team is dedicated to uncovering the secrets of pancreatic cancer’s aggressiveness and then turning this knowledge against the cancer with precision therapies. The lab created a mouse model of the disease that faithfully recapitulates the genetic progression that leads to most cases of human pancreatic cancer. Thanks to this resource, the Hingorani Lab is gaining critical insights into disease biology and rigorously testing new treatments before they advance into human trials. He is also on the vanguard of developing new models of care and clinical research that serve patients’ needs.
Most of all, colleagues said, Hingorani has a deep zeal for his work and great compassion for the patients he serves.
Hingorani has “the passion, the fervor, the burning desire to cure this most fearsome of cancers,” Dr. John Potter wrote in prepared remarks. Potter, director emeritus of the Hutch’s Public Health Sciences Division, played a major role in recruiting Hingorani to the center. “Sunil is a man with a heart of molten silver: bright, hot, and reflecting the very best a researcher can be.”
For Hingorani, the toll of pancreatic cancer is all too real: His father died of the disease.
Among the guests at the reception were many members of Hingorani’s family, including his mother, Kamla Hingorani, whose passion he credited for inspiring his own. He recalled her words on the day that doctors told the family that they were out of options for his father and he had only a few weeks more to live: “You have to make it so that no one ever has to hear those words again.”
Hingorani’s father was a civil and structural engineer, the scientist said, making his new partnership with the Raisbecks especially fitting. James Raisbeck founded Raisbeck Engineering, a firm known for its many innovations in aeronautics engineering that are still used in aviation today.
As dedicated philanthropists, James and Sherry Raisbeck support numerous causes in Seattle and beyond, including medical research, education and the arts. At the reception honoring Hingorani’s new endowed chair, James Raisbeck said that the couple’s interest in pancreas research arose when he developed chronic pancreatitis and type 1 diabetes several years ago. In addition to the Fred Hutch chair, the couple recently committed to an endowed chair in diabetes research at the University of Washington.
“We’re just absolutely thrilled to be involved,” Raisbeck said.
The gift of the endowed chair funds Hingorani’s research in perpetuity, and it provides unrestricted support that allows the scientist to follow his many new ideas as they arise, said Fred Hutch President and Director Dr. Gary Gilliland.
“These crazy ideas that brilliant people like Sunil have can really make the difference for patients,” Gilliland said.
— Susan Keown / Fred Hutch News Service
The American Society of Hematology, or ASH, today announced that Fred Hutchinson Cancer Research Center’s Dr. Oliver “Ollie” Press, an internationally known expert in lymphoma and other blood cancers, will receive an award for outstanding mentorship Dec. 10 at the 59thASH Annual Meeting and Exposition in Atlanta.
He was selected as one of two recipients of the 2017 ASH Mentor Award for his “sustained, outstanding commitment to the training and career development of early-career hematologists,” according to an ASH news release. The other recipient is Dr. Ronald Hoffman, a professor of medicine in the Division of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai in New York
Press is a radioimmunotherapy researcher and oncologist at Fred Hutch, where he is a member of the Clinical Research Division and holds the Giuliani/Press Endowed Chair. He is also a professor of medicine and an adjunct professor of bioengineering at the University of Washington.
He has mentored more than 70 individuals since the 1980s, including undergraduates, medical students, doctoral students and postdoctoral fellows.
According to the ASH release, “his commitment as a mentor can easily be seen in the impressive number of former trainees who have received career-development grants and have gone on to become leaders in academic medicine and pharmaceutical companies.”
Press’ mentees “uniformly cite his unparalleled generosity with his time and his dedication to mentorship activities as having played a large role in advancing their careers. He is also recognized for the value he places on work-life balance, personal connections and professionalism.”
Press has been a member of ASH since 1995 and has served as an associate editor of its journal, Blood, and on multiple ASH committees, including the Program Committee and the Scientific Subcommittee on Lymphocytic Biology. He is the recipient of numerous awards and honors, including the John Ultmann Award for Contributions to Lymphoma Research, the Lymphoma Research Foundation’s Distinguished Service Award, Ellen Glesby Cohen Leadership Award, and Freundlich Leadership Award.
He is the inaugural recipient of the Oliver W. Press Distinguished MSTP Alumnus Award, an award named in his honor that recognizes a graduate of the University of Washington School of Medicine’s Medical Scientist Training Program. He has also received the Department of Medicine Mentorship Award from the University of Washington.
“ASH is thrilled to recognize Drs. Hoffman and Press for their outstanding mentorship, through which they have trained and inspired the future leaders of hematology,” said ASH President Dr. Kenneth C. Anderson of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute in Boston. “We honor their important role in upholding ASH’s strong tradition of hematology training by preparing future generations of mentors.”
— Adapted from an ASH news release