Partnership with The Broad - Desmoid Tumor Research Foundation
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Partnership with The Broad Institute of MIT and Harvard

Jesse Boehm, PhD, The Broad Institute of MIT and Harvard

DTRF announces its funding of an exciting new research project at the prestigious Broad Institute of MIT and Harvard. Below, Dr. Jesse Boehm, Associate Director of the Cancer Program at The Broad Institute, talks about the project and what we aim to learn from it.

 

Using Genome-Scale CRISPR Screening to Create a Desmoid Tumor Dependency Map

A new research project supported by the DTRF aims to enable clinicians in the future to select the best therapies for each desmoid tumor patient. Recognizing the diversity of desmoid tumors in their biological characteristics and response to treatments, the new endeavor aims to pilot a new reference, termed the “Desmoid Tumor Dependency Map”, that links the genetic features of a tumor with specific vulnerabilities that can potentially be targeted therapeutically.

Creating the desmoid tumor dependency map

The project aims first to produce a collection of desmoid tumor laboratory models with full genomic characterization to begin to address the genetic diversity seen in patients. Using these well-characterized disease models, the team will screen over 6,000 drugs to look for evidence of selective desmoid tumor cell killing. This work aims to complement the Collaboration for a Cure project by helping us gain a genetic insight into differences of treatment response.

Researchers will also simultaneously apply cutting-edge CRISPR-based gene editing technologies to study how disabling every gene individually affects desmoid tumor cell survival. In addition to gaining a more precise understanding of desmoid tumor biology, this work aims to identify additional tumor vulnerabilities to help prioritize future drug development efforts.

Empowering the desmoid tumor research community

This project also aims to produce an inventory of nearly 20 desmoid tumor laboratory models that will be accessible for all scientists worldwide, complete with genomic information and optimal culture instructions to improve reproducibility. The pilot version of the dependency map will also be available for an initial prioritization of existing drugs and drug targets for desmoid tumors. As part of the Broad’s commitment to sharing tools, methods, and data with the entire scientific community, all datasets will be available at the DepMap.org portal, along with user-friendly analytical and visualization tools, to help accelerate progress and encourage collaborations in the field.

Next steps

Completion of this project will be an important step toward more effective therapeutics for desmoid tumor patients. We will gain a better understanding of the scale of future preclinical screening that is required to make reliable treatment predictions for patients. Therapeutics that are already in the clinic may be prioritized for further study based on the results of this project, which will provide strong rationale for future clinical trials. We also hope to learn about new molecular targets to inform and prioritize future drug discovery efforts, and to ensure that desmoid tumors are included in ongoing drug discovery programs currently focused on other diseases.

Read the project’s scientific abstract here.

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