Deforolimus (AP23573)

Deforolimus is another newer drug for addressing Soft Tissue Sarcomas (STS). Aside from ET-743 (Yondelis), there are few alternatives out there since soft tissue sarcoma cases are a minority (<1% new of all new cancer cases in the US) and there is not as much financial incentive to find cures for it compared to the other more common cancers.

There's a good write up on Deforolimus at the Liddy Shriver Sarcoma Initiative website. It's a little technical. The article describes how it was found and developed.


Rapamycin was discovered when sample of soil was taken from Rapa Nui (Easter Island) 35 years ago. Rapamycin was extracted from the soil and since the mid 1970s has been used as an anti-fungal agent. In the 1990s, Rapamycin was discovered to have immunosuppressive effects and in 1999 was approved under the brand Rapamune as an anti-rejection drug in kidney transplants. During the testing as a transplant rejection drug, anti-tumor effects were observed as well. Since then, three analogs of Rapamycin have been developed for use as anti-tumor agents: CCI-779 (Temsirolimus) by Wyeth, AP23573 by Ariad and RAD-001 (Everolimus) by Novartis. These three analogs are known as "mTOR inhibitors". mTOR stands for mammalian target of rapamycin.

How mTOR inhibitors work

mTOR  is a cell-signaling protein that regulates the response of tumor cells to nutrients and growth factors. mTOR also controls tumor blood supply through effects on VEGF (Vascular Endothelial Growth Factor). mTOR inhibitors starve cancer cells and shrink tumors by inhibiting the effect of mTOR.


In 2005, CURE magazine had a little writeup indicating claims by it's maker, ARIAD, that more than one third of sarcoma patients (37 percent) had their tumors stabilize or shrink in response to Deforolimus. Additional benefit with the drug was seen in 72 percent of patients who experienced relief of pain or other tumor symptoms. 

ARIAD is currently running a phase III global trial for patients with metastatic soft tissue and bone sarcomas. The trial is called SUCCEED (Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Deforolimus). It's randomized, double-blind and placebo-controlled. It's scheduled for completion in March, 2011. Full details on the SUCCEED trial can be found here. In addition to that trial, shows 9 other trials for Deforolimus.


In August, 2008, researchers published findings showing that mTOR inhibition also leads to MAPK activation. In other words, while mTOR inhibition fights tumors, MAPK activation simultaneously promotes cancer survival. Researchers are now looking at simultaneously suppressing both mTOR and MAPK to enhance the therapeutic potential of mTOR inhibitors. More can be read here.