Archive for November, 2015

 

Nov 30 2015

Much to Be Thankful For

by at 8:53 am

Even in the face of so much external turmoil – with the memory of Paris fresh in our minds, reeling from the murders of innocents in Colorado Springs, and hearing about all of the world’s troubles in hot spots like Syria and Iraq – it is important to note that experts consider this era to be the safest in recorded history. If that seems impossible to you, remember that there have been no world wars, and few of us spend our days and nights worried about being eaten by predators. But, through the miracles wrought by technology, we are instantaneously made aware of atrocities, limited or extensive, natural or man-made, in real time, and in living color. The troubles of relatively few, however heart-wrenching, become part of our communal information-age experience. Perhaps this is a good thing – all unnecessary suffering is and should be intolerable. But, it can be scary.

Let’s not forget that we live in the most incredible society ever created by humans, with comforts, resources and access to information that would have been unimaginable throughout the long sweep of human history. These benefits would have been restricted (if they were available at all) to the most exalted members of society only a few generations ago. Our ancestors, who worried about staving off starvation, would scoff if told that many contemporary societies have to contend with an obesity epidemic! We are now able to address internal enemies, such as cancer, depression, neurological disorders and heart disease because we have the luxury of knowing that we are pretty safe and well fed. So, we have good reason to give thanks, not only on Thanksgiving Day, but any day that dawns where we and our loved ones awaken safe and well, with the prospects of three (or more!) meals in the day to come, leavened by the blessings of freedom and opportunity.

I am thankful for so many things this holiday season. We kicked off our festivities by having the entire family down to our home for Thanksgiving weekend. Being surrounded by our children, grandchildren and my father was incredibly meaningful. The meal was great, and I rejoiced in the happiness and health of our clan. All that, and I have a great job in a wonderful city. Who could ask for more?

Well, I would have been happier had the Eagles not behaved like turkeys on Thanksgiving Day as they were blown out for the second straight week to a second-rate team. For Philadelphia sports fans, now is the winter of our discontent.

Have a great week.

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Nov 23 2015

Pride and Productivity

by at 9:18 am

I hope you have enjoyed your late autumn weekend. We spent Saturday with our kids and grandkids in Baltimore, and watched the Eagles, Hoyas and Redskins lose on Sunday. I must finally be growing up; while our son David was in agony over the Eagles and Hoya losses, I viewed it with vaguely disappointed detachment. Perhaps it is a residue of the somber events of last weeks, which put sports in their proper perspective.

One of the really nice events for me last week was the visit of Dr. Elana Fertig (aka Isaac’s and Aviva’s mom) to give a talk for the ICBI seminar series. As many of you know, Elana is on faculty at Hopkins and is an R01 funded investigator interested in dynamical modeling of signaling events in head and neck cancer. I surreptitiously took photos of her speaking and sent them to family. She gave such a fine talk that I temporarily found myself lost in her presentation rather than just beaming with pride. It was a great moment.

Another nice moment was the opportunity to welcome Cheryl Dumsick as Phyllis Rand’s successor. Of course, Cheryl had a lot of support from Ann and also from Phyllis, who was there to assist with the transition. Welcome, Cheryl!

I am busy preparing for our EAC meeting, and look forward to hosting the meeting. Having completed my part of the Breast Cancer Systems Biology U54 (with gratitude to Bob Clarke for his leadership of this effort), I am now turning my efforts to breast and pancreatic cancer R01s, and to other large scale funding efforts. Lots to do!

Have a great week and a wonderful Thanksgiving.

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Nov 17 2015

Sad Posting

by at 9:11 am

Last week I wrote about the death of my mother’s first cousin; his funeral in Brussels was on Friday, and was attended by my father, brother and one of my nieces. Little did they know that only a few hours later a plot partly carried out only a few miles away from them culminated in a horrific series of massacres of innocents in the City of Lights. I could not escape the ironic juxtaposition of the peaceful end of life of a child of the Holocaust – the most sustained and chilling example of evil in the Western World in our collective memories – with an act of terror that seemingly targets all the children of Western civilization. This malevolent attack on everything that civilized humanity holds dear, violating the teachings of all of the world’s major religions, reminds me of a familiar enemy. We call that enemy cancer. I began wondering, is there anything we can learn from the war on cancer that could be applied, at least in principle, as civilization confronts barbarism that makes use of 21st century mobility, technologies and weaponry?

How do we treat cancer? When it is possible we excise it or employ a definitive local procedure such as radiation therapy. When the malignancy has not spread, that is usually enough to cure the patient. When confronting terrorism, this would be akin to employing police actions to deal with purely local problems. But when the cancer has metastasized to other organs, we must resort to other strategies.

For example, we can employ chemotherapy. Rarely, a little bit of chemotherapy is curative. Massive doses of chemotherapy, frequently administered in combination, are occasionally curative, but typically at terrible cost. In carefully selected instances (for example, some hematological malignancies) this approach can be life saving. But in many other clinical scenarios resistant clones almost inevitably develop. The analogy of this approach to large scale invasions of so-called hubs of terrorism is rather obvious. Initial tactical success (e.g., a partial or even complete remission) is frequently followed by the emergence of rogue cells of hardened fighters who are superbly well adapted to survive in a new world, and to recruit new converts to the cause. Sound familiar?

So, we have tried to get smarter. Targeted therapy, intended to attack the “wiring” of a malignancy, has been described as delivering molecular “smart bombs” to precisely inactivate the functions of proteins that are critical for the proliferation and survival of cancer cells. In an era when real-life bombings can be directed remotely with the aid of sophisticated technologies and even executed by pilotless weapons like drones, this would seem to represent a revolutionary approach to both cancer therapy and to modern warfare. Indeed, this approach has led to some remarkable successes in cancers such as chronic myeloid leukemia and chronic lymphocytic leukemia, and we have seen remarkable video footage of missiles targeting ventilation ducts in a way once only reserved for science fiction movies. But in lung cancer and melanoma, resistance to effective targeted agents usually emerges quite rapidly. All too frequently we can’t anticipate all of the variations in cancer cell populations and account for every possible rogue that might emerge under the selection pressure of a targeted therapy approach. And there are always unanticipated consequences.

Cutting a cancer out can work, but not when it has spread. Intensive chemotherapy can be helpful, but rarely cures metastatic cancer. Targeted therapy can’t yet address the complexity of cancer biology. Other approaches to manipulate the microenvironment have had some successes. Overall, we have been winning the war (cure rates have improved significantly over the past 40 years), but it has been a hard slog, and there have been many casualties. Many of the successes can be attributed to a combination of reducing high risk lifestyles (such as smoking), early detection (i.e., better intelligence), better technology (improved surgical techniques) and earlier therapy (e.g., adjuvant chemotherapy for post-surgical patients with high-risk for the development for metastatic disease). But while the treatment of metastatic disease has proven to be an enduring challenge, recent advances offer new hope.

We have celebrated the remarkable success of cancer immunotherapy in a gratifyingly large number of cancers. Current immunotherapy approaches typically work in a minority of patients with potentially sensitive cancers, but can work for a long time. The immune responses appear to be impervious to resistance mechanisms. And there is one crucial difference between immunotherapy and other forms of treatment. Traditional cancer therapies directly treat the cancer, and the host is a passive recipient of the treatment. The tumor-bearing host need not learn how to control the cancer, and thus remains ill equipped to deal with the unanticipated consequences of resistance. In contrast, immunotherapy can be viewed as treating the patient so the patient’s own immune system can attack and eradicate the tumor, learn from the experience and prepare for future attempts by any remaining cancer cells to foment an insurrection that we oncologists call a relapse. Imagine an approach to terrorism that used these principles!

I am not a political scientist, and am sure many will find my musings to be naïve. But if the war on terrorism has anything to learn from the war on cancer, perhaps there are lessons to be learned from the stunning successes of immunotherapy.

My thoughts and prayers are with the innocent victims who suffered injuries or lost their lives to senseless hatred on Friday, and to the grieving families and friends who have been left behind. Let’s hope that the coming week is peaceful.

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Nov 09 2015

In Memory of a Remarkable Relative

by at 6:40 am

Greetings on a Sunday night as I wait for the start of the nationally televised Eagles-Cowboys game. I saw some of the painful whipping the Patriots gave to the Redskins, though the Redskins have plenty of sorry company during this season of domination by the Patriots.

Last week was interesting and packed with lots of important activities. I genuinely enjoyed participating in the annual GUMC Fall Convocation, and was delighted to see Lombardi well represented in the honorees, most notably Jeannie Mandelblatt, who received recognition for her outstanding research. I spent Wednesday up at the NCI, at the Clinical Trial and Translational Research Advisory Committee (CTAC) meeting. This body helps to set the agenda for the national clinical trials effort, and the scope of activities is quite breathtaking. On Friday my work day was highlighted by the Lombardi American Cancer Society Mini-Symposium, where three of our talented junior investigators gave outstanding presentations of their ACS institutional-grant-supported research. As soon as the symposium ended I headed out to National Harbor to attend the scientific sessions at the Society for Immunotherapy of Cancer’s (SITC) 30th anniversary meeting. This meeting, which could have been held in a cloakroom only a few years ago, had 2500 attendees and an extraordinary array of presentations that underscored the blossoming of the field. I attended another day of SITC meetings on Saturday, and returned home in the afternoon to dress and then drive up to Baltimore with Harriet and Jeff and Betsy Toretsky for the Childrens’ Cancer Foundation Gala. Both Jeff and Aykut Uren received well-deserved awards, and I was pleased to be able to congratulate them for their accomplishments. This was a very nice event, but I was pretty tired by the time we got home at midnight.

The evening’s pleasantries were undercut by a call I received from my father. My mother’s first cousin, Willy Bok, had died unexpectedly in his home in Brussels, Belgium at the age of 81. I first met Willy when I was six years old and my family traveled – by boat! – on the then-glamorous SS United States – now rotting in dry dock in Philadelphia one step ahead of the scrap heap – to Belgium to meet my grandparents and the rest of my mother’s family. Willy, a professor at the Free University of Brussels, was a kind, gentle man. When I confidently told him that the United States had the most people in the world, he patiently talked with me and eventually convinced me that indeed, China had a larger population. He was a gifted teacher. And he was alive because of my mother.

During World War II my mother’s family went into hiding during the German occupation to avoid arrest and deportation to concentration camps. My 12-year old mother was dispatched to a convent under an assumed name and was being trained as a novice for about six months until she was reunited with her family – only the Mother Superior knew the truth that little ‘Isabelle Lambrecht’ was in fact Jewish. My mother communicated with her family by letters from the convent – of course they all had assumed names as well. She was lonely and scared, but the Mother Superior saved her life, though my mom proved resistant to efforts to convert her.

One day my mother received a letter from one of her contacts, letting her know that her little first cousins, Ginette and Willy, had been captured by the Germans and sent to a deportation holding area near Brussels. They were children, and would have been murdered immediately upon arrival to Auschwitz. Their parents did not know where they were, and were frantic. My mother got word to her father, who told the children’s parents where the the kids were located. Their parents went to the holding area, bribed some guards and got their children out, just in time. It is an unbelievable story, and it is true. Fifty years later, both Ginette and Willy flew to the United States for my mother’s funeral.

I feel a connection with Willy that goes beyond that of a distant, elderly relative. He has been a direct link to my family’s narrative, to my mother’s life and to my identity. While he will remain so for as long as I live, another living connection to my history has been lost.

In these uncertain times we are confronted by daily news reports documenting the atrocities and human suffering imposed by senseless violence around the world. Willy’s story is a stark reminder that each of these reports involves human suffering, fear, courage and, all too often, savagery. Not all of these stories have happy endings that allow children like Willy to lead full, productive lives.

I try to live my life in a way that honors Willy’s memory and all those who suffered and sacrificed so I can have a chance to make a difference. Every moment matters. And so does every person. Rest easy, Willy.

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Nov 02 2015

The Washington Monument Retires

by at 7:21 am

Good evening on a pleasant Sunday night. Harriet and I are returning from a brief trip to New York with friends to have dinner, check out the Picasso sculpture exhibition at the Museum of Modern Art and to see a musical (Hamilton, which was fabulous). But when I come to work on Monday morning, it just won’t be the same. Phyllis won’t be there.

Phyllis retired on Friday, and true to her non-mushy nature and desires, there was no particular fuss, and there were no tears. But, make no mistake about it, Lombardi lost a bit of its heart and soul on Friday afternoon. I hardly know where to start when describing Phyllis, and what she has meant to me and to so many others here at Georgetown over the years. She has served as our tough-on-the-outside, tender-on-the-inside confessor, friend, dispenser of tough love, memory and conscience for so many years. I can’t imagine anybody who could have made Harriet’s and my exciting but somewhat traumatic relocation to DC more comfortable, supportive and welcoming.

I am not going to go into great detail, but here is just one story I can’t resist sharing with you. In late 2007, as I was finalizing my agreement to move to Georgetown, I ran into Bob Young, the former President of Fox Chase Cancer Center, and before that, the chief of the medicine branch of the NCI, where Phyllis had worked as Marc Lippman’s assistant. I mentioned to Bob that I brought him greetings from Phyllis. So, Bob, who is as self-confident and unflinching as anybody I have ever known, heard her name for the first time in 20 years. His eyes widened, his jaw slackened, he reeled backwards a bit, and said, “Oh, Phyllis. She’s a force of nature!”

And that she is. When I think of her, so many words come to mind: loyal, outspoken, fierce, caring, smart, demanding, professional, protective, organized (in her own way), messy (oh, that cubicle of hers!), giving…. I could go on, but you get the point. She is not only a force of nature, she also is one of a kind. It has been an honor and privilege to work for Phyllis!

Phyllis has retired, but is not really gone. She’ll be in the office a couple of days per week for the next few months, helping out with the transition as we welcome Cheryl Dumsick as her successor – nobody can replace Phyllis, but I am sure Cheryl will do a great job, with Ann at her side.

Phyllis, I am sure I speak for your legion of friend and admirers when I say that your next act will be a great adventure and I look forward to seeing you frequently and hearing all about the wonderful things you are doing. Lombardi will never be the same without you, but without you Lombardi would never have become the wonderful place it is. Thank you, from the bottom of my heart.

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