The Seattle - Portland Connection

We are grateful to the basic scientist and clinical researchers at the University of Washington, Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center for meeting with our OSHU team (Suman Malempati, Chris Ryan and I) to discuss areas of synergy between our research programs.  We found strong common interests, particularly in the areas of (1) understanding how medulloblastomas grow and spread, (2) defining the basic biology of the differentiation defect for rhabdomyosarcoma and (3) translating recent studies of adolescent and adult sarcoma biology to clinical trials.  The opportunity to explore immunotherapy for sarcomas is especially strong, too.  We are thankful to the laboratories of Dr. Jim Olson, Dr. Stephen Tapscott, Dr. Michael Jensen and the clinical trials researchers Doug Hawkins, Robin Jones, Eve Rodler - and especially surgeon-scientist Chappie Conrad, for taking the time to explore and initiate these dual city collaborations in the Pacific Northwest.  
    
Charles
  

Tissue Banking - Demystified

A question sometimes asked is how research can be advanced, and contributing tissue to a tumor bank for research is a key element (money, yes, is nice... but high quality tissue from patients with tumors for which little is know is more valuable).  And if it can be put in a gentle way, tumor tissue from the patients that researchers and clinicians so far have failed is the most valuable.  That is, tissue from patients with relapses... even post-mortem biopsies from patients that have failed our best treatments.


How does one enroll to give tissue? In the case of soft tissue sarcomas, the Children's Oncology Group (COG) has had a tumor bank protocol called "D9902" open since March 1999.  The consent form for this study is usually presented to families at the time a child is diagnosed and is being considered for a COG treatment study.  Most people think of D9902 as a study for collecting tissue from the original untreated tumor, but... the protocol does already allow tissue to be collected from biopsies done at the time of relapse, as well as tissue taken after death (autopsies, partial autopsies and post-mortem biopsies).  In practice, relapse samples rarely are collected (there are practical reasons not to subject children to extra procedures).  Post-mortem samples are scarce... maybe none, with recent notable exceptions.


Where does the tissue go?  well, a really good tumor bank!  The COG contracts the Pediatric Cooperative Human Tissue Network (pCHTN) to store COG sample studies.  Their Director is Dr. Nilsa C. Ramirez, and she and the Biopathology Center for the pCHTN are at the Nationwide Children's Hospital in Columbus, Ohio.  Nilsa succeeds the late Dr. Stephen Qualman, who himself was taken by pancreatic cancer.  Dr. Qualman was a leader in rhabdomyosarcoma pathology research, but Nilsa keeps this tradition in sarcomas strong, and she was recently joined by rhabdomyosarcoma researcher Dr. Peter Houghton who is building an exciting pediatric cancer research program at Nationwide.


What happens with the tissue?  It gets used, hopefully!  Dr. Stephen Skapek at the University of Chicago leads the Soft Tissue Sarcoma Biology subcommittee of the COG.  Researchers send the pCHTN/COG applications to use the tissue. The applications are reviewed by Steve and others on his committee (such as myself).  If the study looks promising, a few samples are sent.  If the researcher shows promising results, many more samples can be sent.  In fact, for the best studies we even consider, "emptying the bank".  (important notes:  the researchers only have de-identified samples... they won't know each patient's name.  Also, statistical rigorousness is another important judging criteria for proposed studies).  


How much does it cost?  In theory, it shouldn't.... the tissue collection kits are meant to be a part of the existing COG D9902 protocol.  However, there have been cutbacks in what the NIH/NCI gives COG for its studies. If there were a sudden 'flood' of samples, the pCHTN and I estimate it would cost  $150 total (70 for the kit, 30 to ship the kit to the child's hospital, 50 to ship it back on dry ice).  I've talked with a few foundations on whether they'd sponsor kits, and while we don't have any definite commitments, I think if the need arose we could find a way that patients wouldn't need to use their own money to contribute to research through the tumor bank.


I hope this helps with some of the questions arising lately. Feel free to comment on this blog or email me for more information.  


Sincerely,
Charles




   

Welcoming Nicolle!

We are proud to welcome Dr. Nicolle Hofmann to the Keller laboratory as our 2010/2011 Scott Carter Foundation Fellow at OHSU.  Nicolle will be pioneering an osteosarcoma therapeutics study between OSU (Corvallis) and OHSU (Portland).  To this project Nicolle brings a background in plant genetics, which is probably very appropriate for certain kinds of therapeutics we will be exploring.  


Nicolle's bio, in her own words:


" I received my B.Sc. in Animal Sciences at the University of Illinois. After taking a couple years off from school to work as a research assistant in the Nutrition and Food Science laboratory of Dr. John W. Erdman, I went on to pursue a Ph.D. in Plant Breeding and Genetics. Since completing my Ph.D., I have held two post-doctoral positions, one in the Soybean Genomics and Improvement Laboratory at the USDA in Beltsville, Maryland and one in a plant metabolic engineering laboratory at Virginia Tech in Blacksburg, Virginia. Now that I am here in Portland, I am very excited to enter a very important area of research in the Pediatric Cancer Biology Program at OHSU."


Welcome, Nicolle!
   

Scott Carter Foundation Big Show! and Golf Tournament

Jinu and I were privileged to attend and participate in the Scott Carter Foundation fundraiser events this weekend in Tulsa, Oklahoma.  This is an all-volunteer driven two part event, the Big Show dinner and auction, and the Indian Springs Golf Tournament.  It was my pleasure to meet the numerous proactive benefactors of the SCF in Tulsa, including some special parents of childhood cancer survivors including Amy White, a tireless advocate of families in her role as Pediatric Oncology Coordinator of the Oklahoma Family Network.  In its 17th year, this event exemplifies the commitment of a Scott's Family, and his community, to honor his memory by building a stronger foundation of research in childhood cancers. We are grateful that Jinu could be the 2009/2010 Scott Carter Fellow at OHSU.  
  
Charles


[ above right:  John Grant, Paula Carter, Jinu Abraham ]
[ below right:  Jinu Abraham, Cason Carter, Charles Keller ]
   

an informal word on our lab's research

Our laboratory focuses on long term and near-term treatments for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. To say long term, we mean basic science investigation of how these tumors work – such things as what kind of normal cell gives rise to one particular kind of cancer. And in saying near-term, we mean finding molecules in these cancers to directly turn off or turn on by drugs so that the tumor stops growing. Behind both approaches are some rather exciting genetically-engineered mice… modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. Then the tumor can be followed to see how it grows and spreads… even to test a treatment to see whether the tumor growth can be reversed. That these mice have normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

While this use of mouse models makes our lab slightly unique, our greatest asset is that we have a very multi-disciplinary team. Biomedical engineers for building and operating imaging and diagnostic instruments, biochemists for understanding the molecules, molecular biologists and electrical engineers for understanding how tumors express genes in certain ways, and me (the board-certified pediatric oncologist) helping bring it all together in a focused way. Sometimes we venture beyond the ordinary, such as the use of 26¢ fertilized quail eggs (instead of mice or petri dish experiments) to study anti-cancer drugs. That last project is one graciously sponsored by the Alex’s Lemonade Stand Foundation. We’re even the first to work with the National Cancer Institute’s Pediatric Preclinical Testing Program to try exciting new drugs right out of the pharmaceutical development pipeline in genetically-engineered mouse models of childhood cancer.

I’d like to think that tangibly better treatments for rhabdomyosarcoma and medulloblastoma can be found in a matter of years, instead of tens of years. I go to a fundraiser golf tournament for the Scott Carter Foundation every year. They sponsored my research training in Mario Capecchi’s lab years ago, and now sponsor our pediatric cancer researcher in training, Nicolle Hoffman. Standing at the 18th hole every year, I get the same question about every 5 minutes, “Doctor, do you have anything new for these kids yet?” These questions led my lab to put a heavy emphasis on therapeutics about 4 years ago. As a result, we’re finding drug targets, as well as drugs to hit those targets that are less inclined to result in relapse for our patients (ok – yes, it’s just mice so far, but I also am a member of the Children’s Oncology Group committee that designs COG trial for rhabdomyosarcoma).

What's on the horizon?  A lot!  In moving to OHSU in Portland we're now teaming with Dr. Brian Druker to develop personalized targeted therapies (of the non-chemotherapy variety) for children with cancer.  Our results can move faster than ever from the bench to the bedside with the COG Phase I pediatric oncology program here at our Doernbecher Children's Hospital, and with the leadership opportunity of building a de novo Pediatric Cancer Biology Program at OHSU, there's tremendous potential to build a focused team of laboratories that share a common goal of doing the best research and moving making results relevant to patients in the here and now.

Where there is a will, there is a way. Change can be tangible.  And we are accountable.

Charles Keller, MD
keller@ohsu.edu

OSU College of Veterinary Medicine

We thank Dr. Bernard Seguin (oncological surgery) and Dr. Shay Bracha (oncology) for meeting with us today to discuss the intersection of childhood and companion pet clinical trials for cancer.  The specialized facilities at the Oregon State University College of Veterinary Medicine are truly outstanding, and represent a strong resource for partnerships in developing new treatments for soft tissue and bone sarcomas of childhood and adolescence.  


[ above right:  Jinu, Bernard, Charles & Elaine at OSU ]
[ note: neither Ducks or Beavers were harmed in the pursuit of this collaboration ]
  

The “Creating Hope Act of 2010” S.3697

This important proposed bipartisan legislature by Senators Sam Brownback (R-KS), Sherrod Brown (D-OH), and Al Franken (D-MN) would encourage pharmaceutical companies to develop new drugs for rare childhood diseases, including cancer.  Essentially, the pharmaceutical companies would receive a voucher to expedite FDA approval.


For more details, visit Nancy Goodman's website for KIDS V CANCER.