When it’s Time to Put Your Pancreatic Cancer Patients on a Diet

Last week, I had a discussion with a friend and colleague regarding our work and its application to cancers of almost every stripe. During our chat, I received a call from the infusion center requesting the clarification of an order. I responded to the nurse’s inquiry and returned to our conversation. Apropos, my guest inquired whether I ‘d had much success in pancreatic cancers. I smiled and explained that the call I had just received was regarding a patient with that exact diagnosis who is now approaching the one-year anniversary of our first meeting in June 2010.

At 59 years of age, the patient found himself diagnosed with pancreatic carcinoma that had virtually overtaken his liver. Visits to his oncologist and subsequent second opinions at UCLA and City of Hope offered few options. He returned to my care and we conducted a biopsy to examine his drug response profile. The patient could hardly have been more ill. Uncontrollable pain, abdominal distention, a liver that extended almost to his pelvic brim and tumor markers in the thousands that were doubling ever one to two weeks. We certainly had our work cut out for us.

I remember starting his treatment and leaving town for a week to attend the American Society of Clinical Oncology meeting in Chicago. After my departure, I was informed that his CA 19.9 (on his first cycle of therapy) had continued upward, cresting at 6,000 (normal is 0 — 30). I was greatly disappointed by the news. Pancreatic cancer is hard to treat, but I had felt confident that this patient would respond. And then, his pain diminished and he started winding off the industrial doses of narcotics that he had once required. His appetite and exercise tolerance both improved as well. The tumor markers began falling precipitously. And, over the coming month, that giant liver returned to normal.

The best news was the PET/CT that confirmed his dramatic response. The better news still, the subsequent PET/CT that revealed virtually complete resolution of all measurable disease. Oh, and yes, the normalization of the tumor markers.

I turned to my guest and said, “Yes, we can even fix pancreatic cancer in some patients. Would you like to meet one?” We walked together to the infusion center and I introduced the patient to my friend. As the patient sat receiving the final hydration of his, now maintenance, therapy, I realized how much weight he had gained. In fact, I said only half jokingly, “I’m going to have to put you on a diet.”

Now, there’s a change, a pancreatic cancer patient a year after diagnosis for whom my principle current concern is his weight gain. Weight Watchers anyone?

America’s Best Steakhouses? Caveat Emptor (Buyer Beware)

Readers who have traveled by air in recent years will be familiar with sections that appear in the airline magazines, heralded by a banner reading “America’s Best Steakhouses.” Listed beneath this marquis will be a number of restaurants in cities around the U.S. When I’ve examined these lists, I often find restaurants that I recognize, some of which do not represent, in my mind, the best steakhouses. More to the point, some of the most famous steakhouses in the country never seem to appear. More recently, I’ve begun to see America’s best plastic surgeon, America’s best orthopedic surgeon… with glossy photographs of white-coated physicians describing their practices and locations.

Putting two and two together, I’ve come to realize these are little more than slick advertising schemes. In essence, the magazine offers you the moniker of “best” in your field if you pay them a fee. Furthermore, it appears that the quality of your work goes up the more you pay. Perhaps “America’s most self promoted” should replace the word “best” in these lists.

While the magazine editors, no doubt, defend this by explaining that they vet each potential participant, it seems unlikely that the size of the photograph actually correlates with the quality of the doctor. Based on what I can see, the doctor’s “quality” is most closely associated with his willingness to pay. This modus operandi is becoming more common, as several national magazines now list the best hospitals and best physicians under similar circumstances.

Recently, I was approached by one prominent national magazine and offered the opportunity to participate in a best doctors’ feature, but I declined. Nonetheless, if anyone reading this blog is desperate to see a glossy photograph of me listed among the country’s best doctors, simply forward $65,000 to my address and I’ll be happy to comply. And I promise to remember to smile.

Chocolate-dipped Fresh Strawberries

I returned from the hospital late-morning on Monday, May 2, to find a tray of succulent, ripe strawberries, dipped in dark chocolate. When I inquired the source of this largesse, I was informed that it was a celebration. My very sweet patient, Sue Allen, had brought us these lovely desserts in recognition of her sixth anniversary. It is now six years since this charming Neonatal Intensive Care Unit nurse presented to my attention with widely metastatic non-small cell lung cancer.

I remember, as if it were yesterday, sitting across from her and her husband and examining the dreadful findings on her CT scan: “Hilar mass, extensive bilateral mediastinal adenopathy, bulky right supraclavicular andenopothy.” When we met, I had no idea what lay ahead. We were meeting for the first time and I had yet to run a study to explore treatment options. The gratifying good outcomes since then reflect her very favorable laboratory profile results.

On Monday, Sue was in and out of the lab before I could see her and congratulate her on this momentous occasion. But, I know how well she is. Her most recent family ski trip to the Sierras a few weeks ago once again reminds me that even the worst cancers can be beaten back. Although she has suffered recurrences, we have succeeded in controlling every new area of disease. While there have been compromises and hardships, she leads a normal life, raising her 10-year-old son and enjoying social and sporting activities with her family and friends. It is difficult to imagine what might’ve happened to Sue had we not met and determined her best treatments from the onset of her disease.

What I can say with certainty is that there’s something particularly sweet about those strawberries knowing the significance for Sue, her family and all the patients with lung cancer.

Has the Era of Genomics as we Know it Come and Gone?

I have often described my personal misgivings surrounding the application of gene profiles for the prediction of response to therapeutics. My initial concerns regarded the oversimplification of biological processes and the attempt of analyte-driven investigators to ascribe linear pathways to non-linear events.

The complexities of human tumor biology, however vast, took a turn toward the incomprehensible with the publication of a lead article in Nature by the group from Harvard under Dr. Pier Paulo Pandolfi. (Poliseno, L., et al. 2010. A coding-independent function of gene and pseudogene mRNAs regulates tumor biology. Nature. 2010 Jun 24; 465(7301):1016-7.) I sat in as Dr. Pandolfi reviewed his work during the Pezcoler Award lecture, held Monday, April 4, 2011, in Orlando at the AACR meeting.

What Dr. Pandolfi’s group found was that gene regulation is under the control of messenger RNA (mRNA) that are made both by coding regions and non-coding regions of the DNA. By competing for small interfering RNAs (siRNA) the gene and pseudogene mRNAs regulate one another. That is to say that RNA speaks to RNA and determines what genes will be expressed.

To put this in context, Dr. Pandolfi’s findings suggest that the 2 percent of the human genome that codes for known proteins (that is, the part that everyone currently studies) represents only 1/20 of the whole story. Indeed, one of the most important cancer related genes (known as PTEN, is under the regulation of 250 separate, unrelated genes. Thus, PTEN, KRAS and, for all we know, all genes, are under the direct regulation and control of genetic elements that no one has ever studied!

This observation represents one more nail in the coffin of those unidimensional thinkers who have attempted to draw straight lines from genes to functions. This further suggests that attempts on the part of gene profilers to characterize patients likelihoods of response based on gene mutations are not only misguided but, may actually be dishonest.

The need for phenotype analyses like the EVA-PCD performed at Rational Therapeutics has never been greater. As the systems biologists point out complexity is the hallmark of biological existence. Attempts to oversimplify phenomena that cannot be simplified, have, and will continue to, lead us in the wrong direction.