DTRF's Groundbreaking Project - Desmoid Tumor Research Foundation

DTRF's Groundbreaking Project

Update- May 2016

Dr. Ben Alman and collaborators on this project have already identified six drugs that show promise as potential therapies (Dasatinib, an oral Bcr-Abl tyrosine kinase inhibitor; a multi-targeted PI3K inhibitor; an FAK inhibitor; and, Letrozole, a gamma secretase inhibitor).  In addition, they recently discovered that a therapy that possibly could be applied rapidly to patient care is the use of glucocorticoids.  Dr. Alman states, “This treatment significantly decreased tumor burden in treated mice.  Glucocorticoid drugs are currently being used along with traditional chemotherapy in leukemia, and in that disease adding the glucocorticoids substantially improved survival.  We will present more on our preliminary work on this at the DTRF Annual Patient Meeting on September 24, 2016.  Our ongoing work is testing the drugs in combination, towards the goal of developing an effective multi-drug regimen. Our finding that glucocorticoids inhibit tumor burden, raises promise that these drugs can be added to other therapies, much in the same vein as this drug family’s use in leukemia, substantially improving outcome.”


The Desmoid Tumor Research Foundation has initiated a groundbreaking collaborative drug screen research project, “Collaboration for a Cure, Identifying New Therapeutic Targets for Desmoid Tumors.” The goal of the project is to streamline and vastly accelerate the search for new effective desmoid tumor therapies. By facilitating the collaboration of top scientists and research institutions, we look forward to exciting new discoveries.

Each collaborating institution will take a particular part of the project in which it has the highest expertise and all collaborators will share data and build on each other’s discoveries. It is estimated that years of research time can be saved by multiple institutions collaborating in this manner.

The following summary of the project was written by two of the collaborators, Benjamin Alman, MD, of Duke University Medical Center and Robert Maki, MD, PhD, of Monter Cancer Center. The other collaborator is Alex Lazar, MD, PhD, of MD Anderson Cancer Center.

Desmoid tumors are difficult to treat using conventional therapies. One approach to treatment is to develop a multi-drug therapy of a number of agents that target different biologic aspects of tumor growth, but have few side effects. The use of a targeted multi-drug approach could stop the tumor cell growth or kill tumor cells without causing serious side effects.

DTRF’s “Collaboration for a Cure” project will screen libraries of available drug agents to identify those which inhibit desmoid tumor cell growth but not normal fibroblast cells.

DTRF has previously funded a screening of 1,000 drug agents in desmoids undertaken by Dr. Benjamin Alman. That screen identified one agent, nefopam, which is effective in inhibiting desmoid tumor growth in mice. Nefopam is being further studied and is moving toward a clinical trial in Canada. The exciting success of this initial screen of 1,000 agents showed that screening is a productive approach to identifying effective anti-tumor agents.

The agents identified in the new screen of agents will be analyzed for pharmacokinetic properties that would suggest agents that can be successfully used in combination. These combinations will then be tested in human desmoid cell cultures and mouse models. Effective combination therapies that are identified would then be tested in patients.

The agents will also be analyzed to determine their underlying biologic mechanism to identify new pathways that are activated in beta-catenin in desmoid tumors. This data will be used to inform new research into the biology of how beta-catenin causes desmoid tumors.

This project is expected to rapidly identify a multi-drug regimen using agents that are already FDA-approved for patient use, which can then safely be tested for efficacy in patients.

In addition, the project will identify new pathways activated by beta-catenin and new agents not yet in use for patient care that target desmoid tumors, both of which can be developed in future work which might ultimately identify even more effective therapeutic approaches.

This project is uniquely possible because of the initiative and funding of The Desmoid Tumor Research Foundation. This type of drug screen is commonly used in cancer research, and has been done for every common type of cancer yielding many effective therapies. However, such a project is typically funded by large pharmaceutical companies which stand to profit from the resulting therapies that can apply to potentially millions of patients. A drug screen that only stands to benefit a comparatively few patients with a rare disease such as desmoid tumors is not likely to be undertaken for reasons of economics.

Thus, the funding provided by DTRF is critical to move this research forward. By combining our areas of expertise in multiple institutions, and with multiple streams of research taking place simultaneously and in collaboration, we will be able to cut years off of the process of solving the puzzle of desmoid tumors and developing effective therapies.