Fenretinide and ABT-751?

I have been having a horrible time writing the latest article concerning my trip to the ANR in Japan. It is driving me absolutely batty. I have put it down and picked it up more times than I care to reflect. The irony is that in reality it really should be so easy me to author. Truth be told, I probably know more about this particular subject than I know about anything else in the world of neuroblastoma. I think the biggest problem is that it is a subject that is so often misunderstood on many different levels. I can't tell you how many people I have talked to that have completely missed the boat on the key points that you really should know about the drugs - good or bad. Parents get so wrapped up in asking the ultimate question of whether a drug works or doesn't (rightly so), that they forget to really absorb why it works when it does and why it fails when it doesn't. The answers are often missed even though they are right before our eyes. Answers are often found in the subtleties and this understanding could be the difference between a drug or therapy saving your child's life. It is for this reason that before I talk about a combination of drugs that I address the drugs individually. Let's understand why they are important. Why they work? And why they don't? When you understand this you will likely understand when this combination is important and why it could be so incredible. Mark my words, I believe more kids will live because of this combination. Period.

In the end, since I have had so much trouble writing the article I am going to commit myself to do it in my diary. Maybe here, I can get through it. Here goes!

One of the most common questions that I have received since returning from the Advances in Neuroblastoma Research Meeting in Japan is "So did you see any new promising ideas for my son or daughter?" This question mostly seems to come from parents of relapsed children but there is no doubt that the question of what is on the horizon is on the forefront of all of our minds. It might then surprise you if I told you that one of the most promising therapies to come out of the ANR centered around a drug that has been floating around from the 1960s. Most will be shocked when I tell you that I am confident that there is not as striking a set of data anywhere in xenograft mouse models of recurrent neuroblastoma. (Read that again.) You will be floored when I tell you that all of this excitement surrounds a single drug, Fenretinide (4HPR).

The one presentation generating the most excitement was entitled "Fenretinide/Lym-X-Sorb Oral Powder Combined with the Oral Microtubule Inhibitor ABT-751 is Highly Active against Multidrug-Resistant Neuroblastoma Xenografts." In the end, they found that 4HPR and ABT-751 was a well tolerated oral drug combination that was highly active against multiple recurrent neuroblastoma xenograft models. Over the years we, as parents, have seen multitudes of studies showing activity against neuroblastoma. So why is this one so special. In this article I will lay the groundwork to tell you why this discovery is so important and so promising for our kids.

WHAT IS GOOD RESEARCH?
When evaluating any type of abstract, presentation, or medical article there are some very important things to understand. First, there are many different levels of success when it comes to killing neuroblastoma cells. A study may say "kills neuroblastoma cells" but that usually means very little. It is important to note how much neuroblastoma was killed, what type of neuroblastoma cells did it kill, and finally, was the dose of drug used actually achievable in our kids. Simply put, unless the drug kills neuroblastoma a lot faster than it grows, kills in multiple resistant cell lines, and the drug can actually be given to kids in levels that have shown this killing; why would you want to put it into our kids. The US National Library of Medicine is jam packed with medical articles that show drugs killing neuroblastoma cells. However, many of the drugs kill so little of the cell population that the drug would provide little value in our kids. Many, if not most, articles also show drugs killing neuroblastoma cell lines that are so sensitive that water alone could decimate the entire colony. Often drugs are also tested in oxygen rich situations which can be great for killing neuroblastoma cells but are impossible to mimic in the human body. Many drugs are tested at levels that would never be achievable in the human body because they are so toxic they would likely induce death or toxicities so great that it would be unethical to test on any human being. There are many reasons that seemingly good titles on medical articles get us excited but there are also generally far more reasons that the actual research is less than impressive. I tell you this so that you become aware, that you become skeptical, and so you can identify meaningful research. I also use this as a bar and so that you understand that when I explain the findings of this 4HPR/ABT-751 presentation you understand how meaningful and important this research is to our kids.

I have just touched the tip of the iceberg when it comes to potential flaws in research. There are many more areas of concern but this is a good start. For an excellent overview of the ingredients of qualitative research please review the video below. Watch this video on video.google.com.


This purpose will be continued...