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P13K Inhibitors Excite Researchers – Found To Work In Some Blood Cancers

Home/P13K Inhibitors Excite Researchers – Found To Work In Some Blood Cancers

P13K Inhibitors Excite Researchers – Found To Work In Some Blood Cancers

One of the challenges of managing an information oriented site like this one is how best to speak to a wide variety of readers, all with very personal needs and interests.  Become too technical and you keep experienced survivors happy at the expense of those who desperately need information most–those who have been recently diagnosed–or had loved ones diagnosed with multiple myeloma. 

It is easy to get caught-up in all of the new, abstract research and forget to re-visit the basics–something I should keep in mind as I cover the ASH conference in Orlando this weekend.  I want to give a shout-out to all of you newly diagnosed multiple myeloma patients and caregivers out there!  But this article is not for you.  The name of the site where one of our readers found it should give you a clue:  Seeking  One of our readers?  Yes!  Some of our best article ideas come from you.  Thanks for that!  Now, on to the technical stuff…

Drug Development Spotlight: The mTOR’s New Clothes?
by: Michael Becker November 23, 2010

In 1837, Hans Christian Andersen authored a short tale titled The Emperor’s New Clothes. The main character, so enamored by his appearance and his clothing that he had a different suit for every hour of the day, was swindled by a pair of weavers purporting that they could create clothing from a magical fabric that would only be visible to those who were completely pure in heart and spirit. However, when the Emperor parades before his subjects in the new outfit, a child cries out “But he isn’t wearing anything at all!” The Emperor had no clothes.

The tale seems fitting to illustrate the evolution of drugs that target the phosphatidylinositol 3-kinase [PI3K] pathway [see Table 2 for a listing of compounds in clinical development]. Despite ample evidence that pan-PI3K inhibitors and dual PI3K/mTOR inhibitors might offer a therapeutic advantage, tailors continue to weave new compounds targeting individual components of the pathway with presumably superior properties. But does the “mTOR” really have new clothes?

This is a long and very detailed article.  Here is a link back if you would like to read it in its entirety.  Let’s jump forward and view another excerpt from the last page:

In contrast, significant responses in hematological cancers have been reported with PI3K inhibitors. For example, Calistoga Pharmaceuticals’ delta selective PI3K inhibitor CAL-101 demonstrated overall response rates of 57%, 67%, and 30% in indolent non-Hodgkin’s lymphoma [NHL], mantle cell lymphoma [MCL], and chronic lymphocytic leukemia [CLL], respectively. However, in acute myeloid leukemia [AML], multiple myeloma [MM] and diffuse large B-cell lymphoma [DLBCL] there were no responses and no stable disease. Accordingly, several pan-PI3K inhibitors and dual PI3K-mTOR inhibitors are advancing clinical development in the responsive B-cell malignancies both alone and in combination with potentially synergistic agents. Updated clinical data from various PI3K inhibitor programs is expected at the upcoming American Society of Hematology [ASH] annual meeting held December 4-7, 2010, in Orlando, FL.

No multiple myeloma related response?  Why bother?  Other research I have read speaks favorably about these inhibitors when used in combination with other novel, established novel therapy agents.

Its all about combination therapy these days.  But discovering which combinations work best in which patients isn’t easy.  As author Michael Becker states in the article, “Developing one investigational drug is challenging enough, but developing two investigational compounds simultaneously can be daunting.”

Good thing researchers now have powerful computers which can speed up pre-clinical combination research.

I leave for ASH tomorrow.  I can’t wait!  But I promise not to get so involved with all of the technical developments our newer readers feel lost. 

Feel good and keep smiling!  Pat