Archive for September, 2014

 

Sep 28 2014

Setting a deadline on life

by at 7:44 pm

It must be my fault. Both NFL football teams I follow – the Eagles and the local guys – lost this past weekend. The Redskins loss, while humiliating, at least was thorough–no reason to agonize over one or two plays. The Eagles, as is true every week, give their fans a serious stress test. This time, there were no celebrations to be had. But, there is always next week.

On another, completely unrelated note, I came across a very interesting article this weekend in the Washington Post titled, “Why set a deadline on life?”

Basically, Zeke Emmanuel, whom I know a bit, thinks he (and by implication, everyone) should not aspire to live past 75! That sentiment, and the thoughtful response by Ruth Marcus (the article attached to this blog) set me to thinking about my father, who will turn 88 this December. He is a patent lawyer who worked full time until about 3 years ago, and still gets into his office in New York City from time to time. Over the past year or so he has begun to physically slow down, but he still is quite active, reads voraciously, completes the New York Times crossword puzzle every day (in ink), and generally has a ball.

No doubt there is room to more thoughtfully apportion health care to the elderly to minimize toxic, costly and ineffective care that does not improve the quality or length of life. However, the dangerous implication of Zeke’s position is that he is a prominent ethicist and policy advisor. Left unchecked, his blanket “prescription” could actually generate momentum to deny care to the elderly without considering them in the full context of their lives. If we are serious about personalized health care, shouldn’t we consider the patient in his or her totality? Perhaps one’s age is less important than one’s health and vigor. And who can really estimate the impact of a blanket policy that is the antithesis of personalized medicine? One way to think about this issue is think about potential losses if we changed our approach to health care for the elderly.

To test this idea I made a list of what my father would have missed had he lost many years of continued mobility–with its beneficial impact on his survival and quality of life–without the opportunity to have a hip replacement when he was getting older.

He would have missed (among many other pleasures):

  • 10 years of working full time in a high impact, satisfying job
  • Celebrating the Phillies World Championship in 2008 with me
  • Watching his granddaughter sing the so-called 11:00 number (the climactic solo) on stage in a hit Broadway show
  • Dancing at the weddings of two grandchildren, with another wedding on the way
  • Watching his son hood his grandson at his medical school graduation
  • Welcoming two great grandchildren into the world, one of whom is named in honor of his late wife
  • Traveling around the world with long time companion
  • Sharing countless meals with my brother and sister in law
  • Smoking about a million cigars (over the objections of his gently disapproving oncologist son) and completing almost as many crossword puzzles
  • Cleaning up after his Australian Shepherd
  • Hosting most of our family’s big holiday meals, celebrating life’s events and transitions with his family, and seeing how it all has turned out

And, we would have missed the pleasure of his company.

Zeke has not really thought through his proposition. In fact, I think he is wrong–dead wrong. And I for one am glad he is.

Have a great week.

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Sep 21 2014

Work and a bit of football

by at 5:41 pm

I just finished watching a great NFL football game. The Washington team members are true Warriors (wouldn’t that be a wonderful team name?) and actually deserved to win the game since they dominated both lines of scrimmage, and have a quarterback who can move their team. But the Eagles found a way to win, somehow. I hope the Eagles have an easy game sometime soon, just for a change. I can’t take too many more cliffhangers like this without an occasional break!

After last week’s GU Executive Committee retreat (tragically punctuated by the untimely death of an undergraduate from meningitis), I had the privilege of representing Georgetown Lombardi at a reception at Capitol in conjunction with the Rally for Medical Research. Our legislators are hearing loud and clear about the remarkable promise that will be unfulfilled if support for research is not improved. Ironically, the next morning was highlighted by my participation as a panelist on the Dianne Rehm show on WAMU 88.5, where we talked about recent advances in cancer therapy (you can find the link below).  Let’s hope that the messages get through.

That afternoon, my clinic served as a harsh reality check. My young patient with metastatic colon cancer has experienced a number of setbacks over the past few months, and seeing him reminded me that, even though he is still with us two years and nine months following the diagnosis of metastatic disease, moderate improvements in life expectancy are simply insufficient. We need transformative treatment options that will allow him, and others like him, to experience the joy and satisfaction of watching their children grow to full maturity.

But we can’t make that happen without money. So, I went straight from clinic to the Lombardi Gala Executive Committee meeting where I met with our dedicated and passionate volunteers who are planning this year’s event, which will be held on October 18. I can’t reiterate how important their work is–the Gala has raised over $22 million over its lifetime, supporting countless research projects and innovative ideas that have helped us be successful. My thanks, as always, go to Elena Jeannotte and her team, and to our event co-chairs, Paul Schweitzer, Jill Kilpatrick and Brian Katz. Their belief in our mission is inspiring. So, I think I’ll get back to work now–though I may watch a little bit more football too.

Have a great week.

 

The Diane Rehm Show: “New Thinking about Treating Cancer”

http://thedianerehmshow.org/shows/2014-09-18/new-thinking-about-treating-cancer

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Sep 14 2014

No time to rest

by at 10:22 pm

We really enjoyed the weekend, half of which was pretty rainy, but Sunday was beautiful. I assume fans of the local football team are happy, albeit worried about the injuries to RGIII and DeSean Jackson. However, it seems as if Cousins, the backup QB, made the offense click, so they will be a real challenge when they play the Eagles next week. However, my angst for this week starts on Monday night at around 8:00 pm or so, when the Eagles play the Indianapolis Colts.

The past week was highlighted, of course, by receipt of our Notice of Grant Award for the Georgetown Lombardi Cancer Center Support Grant (CCSG). Even though I knew it was coming for many months, I was surprised to be filled with so much satisfaction upon its receipt. It is an important milestone for Georgetown Lombardi, and is a useful reminder of the progress we have made over the past four years. However, this is no time to rest; in fact, even as I write this blog I do so while reviewing my presentation for our External Advisory Committee meeting next month. The fun never stops!

I spent Tuesday at the National Cancer Advisory Board meeting, talking about the Intramural Research Program’s research priorities. It was very invigorating, and reminded me of the many wonderful colleagues we have as potential collaborators, only a few miles up the road. A few other highlights of the week included the resumption of the Wednesday seminar series; I want to extend my thanks to Anton Wellstein for resuming the series, and to Chunling Yi for her excellent presentation.

This coming week will start with the Georgetown University Executive Committee Retreat, and will be punctuated by various fundraising activities. We also plan to submit a paper describing our functional genomics screening studies in estrogen independent breast cancer this week, so it promises to be a busy one. I hope your week is both busy and good.

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Sep 07 2014

Cancer Immunotherapy, the Game-changer

by at 10:46 pm

The week was shortened by the Labor Day holiday, but it was eventful nonetheless. I had many meetings regarding our budget as we strive to meet fiscal requirements while supporting Lombardi’s scientific priorities. One of the more interesting experiences occurred when I was called by the AACR to ask if I would serve as its spokesperson for media personnel seeking comments regarding the FDA approval of Merck’s anti-PD-1 antibody on Thursday. I agreed, but was unprepared for the deluge of media requests that followed. I felt like a character on a TV show, with my phone ringing off the hook with requests from various media outlets. Karen Teber (Mallet) kept the exercise from spinning out of control; as always, I was grateful for her assistance and guidance. While it was a hectic experience, I was really pleased to be able to share my perspective about an exciting new therapy for melanoma that is likely to be used in many types of cancer in the future.

For those of you who haven’t followed this story of effective, game-changing cancer immunotherapy, it is worth summarizing. It is important to remember that the host immune system is an important enemy of developing cancers, so it stands to reason that successful cancer cell populations have figured out ways to evade, disable or overpower the anti-tumor immune response. Many such mechanisms have been demonstrated, but none are more elegant than the activation of the PDL-1: PD-1 axis. PD-1 is expressed by activated T-cells. Some malignant cells express PD-1’s binding partner PDL-1, which can be induced when an activated T cell spitting out gamma-interferon is in the neighborhood. When tumor cell based PDL-1 binds to PD-1 on T-cells, the T-cells “go to sleep,” thus inactivating the T-cell dependent host anti-tumor response. Essentially PDL-1 provides a “shield” that protects some cancer cells from being killed by activated T-cells that have evaded or slipped through other tumor defenses against immune attack. In its own diabolical way, this is a beautiful story.

Monoclonal antibodies that disrupt the binding of PDL-1 to PD-1 can reverse this mechanism and release the brakes on antigen-specific anti-tumor immune responses. Several anti-PD-1 antibodies are quite active in the clinic, as is at least on anti-PDL-1 antibody. In malignant melanoma as many as 40% of treated patients have major anti-tumor responses to anti-PD-1 therapy, and many of these responses are durable. Such antibodies can be combined with antibodies directed against another immune checkpoint, CTLA4, with even more impressive clinical benefit. And, there are additional immune checkpoints that may prove to be useful therapeutic targets. These agents seem to work in kidney cancer, bladder cancer, lung cancer, and other tumors; the toxicity profiles are quite different from those of standard chemotherapy. So, it now seems that treating the immune system so it can treat cancer is a reality that will change how we do our work in the future.

Georgetown Lombardi is well poised to lead in this exciting new area. Led by Mike Atkins, Georgetown Lombardi is deeply involved in clinical research studies in melanoma and kidney cancer, and many other investigators, such as Beppe Giaccone, Mike Pishvaian and others are studying these agents in other diseases. While my lab has a longstanding interest in immunotherapy, not a week goes by without me hearing about Georgetown Lombardi scientists such as Anton Wellstein, Priscilla Furth, Chunling Yi, and  Bob Glazer who are also finding the relevance of immune modulation in their own research.

Building on the idea that immune selection pressure is a major source of diversity in developing cancers, it stands to reason that this same diversity allows cancer cell populations to develop resistance to other forms of cancer therapy. So, there is room for many Georgetown Lombardi scientists and perspectives in this emerging new field!

Just writing about these exciting concepts and new advances makes me want to go devise some new experiments. So, it’s back to work for me.

Have a great week.

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Sep 01 2014

In memory of Insoo

by at 10:06 am

Welcome back from what I hope was a great Labor Day holiday. I had a wonderful vacation and return to work refreshed and ready for a busy autumn. But I would be remiss in not using this blog to share some reminiscences about my colleague and friend, Insoo Bae, who tragically passed away last week. Obviously, he will be missed as an excellent scientist, colleague and educator. However, I also will miss him for how he opened up a new world for me.

A few years ago, Insoo became involved in a South Korea government-sponsored program known as the “World Class University.” The idea was to have South Korean educational institutions engage leading universities and academicians from around the world to teach and work in South Korean institutions to create opportunities for their students and faculty and to import best practices that could elevate the academic stature of these institutions. Insoo created a connection with Dankook University in Cheonan, and several GUMC faculty were invited to participate as short-term visiting scholars. I went to Cheonan and Seoul a few times to teach cancer immunology and interact with clinical and scientific colleagues, and Insoo was there on several occasions, assuring I was able to navigate a novel and foreign culture as a “resident” as opposed to tourist. He also made arrangements for me to give lectures and establish collaborations with institutions in Seoul, Daegu and elsewhere. One of those visits led to a two-year long collaboration with Samsung Advanced Institute of Technology, which culminated in a nice paper published earlier this year in Oncogene.

Insoo introduced me to a new world, a fascinating culture, and many memorable experiences, including the Korean Museum of Independence, the many fabulous museums and historical sights, the energetic and remarkable city of Seoul, the haunting and sobering DMZ and the chance to meet many wonderful people. However, (and I smile even as I write about this), I will never forget baseball and golf in Korea. On one of my visits Insoo and his son Edward, knowing that I love baseball, took me to see a major league baseball game in Seoul. Everything was familiar, but different; the game was the same but the organized cheering sections were definitely not something one might see at Nationals Park. It was so kind of Insoo to take time out of his family vacation to take me to that game.

It was even more remarkable when he arranged with his brother to take me out to play golf, some two hours-plus away from Seoul. Golf is a huge sport in South Korea, and it is imperative to be appropriately dressed. Naturally, the dress code included proper golf shoes. Now I am a big fellow by Korean standards, and it was pretty hard to find the correct golf shirt and shorts, but it proved impossible to find golf shoes that came close to fitting me, and sneakers were not permissible. Finally, I prowled through Itaewan, the “Western” sector of Seoul, and found a specialty sporting goods store that had a golf glove that fit and a pair of golf shoes that was only two sizes too small for my feet. The next day, I had a marvelous day of golf (though I played horribly, and with feet that hurt) and enjoyed the extraordinary hospitality of Insoo and his brother. Poor Insoo was not a golfer but gamely hacked his way around the course (he was a much, much better scientist and an even finer man). I will never forget his kindness and generosity. I also will never wear those golf shoes again.

Insoo had a vision to elevate Korean science even as he made his life here in DC and at Georgetown. He was, in his gentle and unassuming manner, relentless in pursuing that objective, and thus made the world a better place as a husband, father, scientist, friend and scientific ambassador. I will miss him, but will never think of him without a smile. Rest easy, my friend.

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