Thursday October 9, 2014

The moon has been ever present these past few days.  Bright and full and visible in the morning and at night.  That full moon always leads us back to our last days with Shannon.  Those days when she was losing her battle, when we were making plans for how to celebrate her life and how to honor her wishes.

Shannon made it clear to us that she wanted to matter.  She wanted her life to make a difference while she was here, and after she was gone.  She told us so.  We went to St. Jude so she could be a part of the research.

In those last days of her life, as the moon grew full, we made plans to donate Shannon's tumor cells.  Just hours after she passed away, her tumor cells were harvested by Mayo Clinic pathology. Those cells were sent to Memphis, where they arrived at St. Jude just 24 hours after Shannon had passed away.   Dr. Wetmore was there to start the process of nurturing and growing these cells.  We didn't know where that would take us...

This week, it took us to a lab at the Mayo Clinic.  Upon Shannon's passing, a research group at Mayo Clinic decided to focus a part of their research on DIPG tumors.  Shannon's funeral had a profound effect on Dr. Richard Vile, a PhD in molecular medicine at Mayo, and his wife, Memy, who also works in research.  There's some cosmic karma at work here.  Dr. Vile and his family are acquaintances of mine through my years of teaching tennis.  The fact that they attended the funeral, and after that experience, decided to work on pediatric brain tumors is nothing short of amazing to us.

Dr. Vile's research is in experimental immunotherapies and vaccines to treat cancerous tumors.  They are looking for a systemic treatment option.  Dr. Vile requested and received some of Shannon's tumor cells from Dr. Wetmore at St. Jude.  Shannon's cells actually became a part of the research she inspired.

So, here we are, two years into their research, and the first paper has been published.  We wanted to hear all about it, so Dan Erin and I paid a visit to the research team this week to learn more.  We met the team, and we saw the lab.  They told us that Shannon's cells continue to grow and, in theory, should live on forever.  Live tumor cells are key to the research.  The results so far have been promising, and they are hoping for a $2 million grant to take this research to the next level.

The paper they published in the American Society of Gene and Cell Therapy is way over my head, but I asked Dr. Vile for a layman's explanation of what the research has shown so far.

Essentially, we have found that a tumor growing in the brain acquires an identity which is rather different to that which it has when it is removed from the local environment of the brain. Thus, when we look at brain cancer cells in the tissue culture dish, they express a different profile of proteins than that profile which is expressed in situ in the brain.

This is important (we think) because the profile of antigens that a tumor expresses in the brain is the critical one. It is this profile which forms the basis of therapy targets - such as drugs, immune therapies and so on. So, if therapies are designed based on the profile of proteins seen only when the tumor cells are studies in tissue culture, we may miss some important targets for drug development. 

In Shannon's paper, we have identified some proteins which are expressed on tumor cells only when growing in the brain, and not when the cells grow in culture. We have shown that the local brain cells (macrophages, monocytes) impose this pattern of protein expression on the tumor cells. Therefore, this manuscript raises a new therapeutic approach to target these new, brain expressed proteins on tumor cells - which otherwise would not be considered as drug targets. Finally, we show that by targeting these new proteins we could clear brain tumours from mice.

So, we believe that Shannon's cells are a critical tool here - in culture they show us a certain defensive look as it were; but when we grow them in the brain, they call an audible at the line of scrimmage, and show a very different look (I apologize that I do not know the equivalent hockey terminology). We need to understand and read the defensive shift and target that specific defense with novel therapies.

The one part of the paper I did understand was the acknowledgements.  "This work was inspired by and dedicated to Shannon O'Hara."   

Our visit to the lab gave us a chance to thank these scientists for the work they are doing, to humanize their efforts, to put a face on this painstaking, difficult work.  It was an emotional connection for all of us. Dr. Vile and the research team thanked us for precious gift from Shannon.

That full moon in the sky reminds us of the end, but it also reminds us she's still here in so many ways.  We do our best to carry on your legacy, sweet girl, just as you hoped we would.