Landmark paper reveals new therapeutic vulnerabilities for chordoma

Update 4/6/23: The paper summarized here has now been published in Nature Communications.

In an exciting update, our grantees at the Broad Institute of MIT and Harvard have released a preprint presenting the most complete understanding of chordoma’s genetic vulnerabilities to date. The paper, co-authored by Chordoma Foundation researchers, is the result of a target discovery partnership we embarked on with Broad researchers in 2016 to map all of the genes essential to the unbridled growth of chordoma cells. The goal was to systematically uncover new therapeutic hypotheses for this disease, which could lead to more effective treatments. (In 2019, this project convincingly argued that brachyury is a main Achilles’ heel of chordoma.)

The new preprint reveals a number of potential therapeutic targets for chordoma, which researchers can now follow up on to determine whether they can be translated into treatments for patients.

Importantly, therapies related to one new target the Broad scientists identified in chordoma cells — called SHP2 (pronounced “ship-two”), which regulates multiple cancer-driving processes — are immediately available to chordoma patients with advanced disease. As shown in the paper, we deployed our Drug Screening Program to evaluate drugs targeting SHP2 in mouse models, where we observed strong anti-tumor activity — in fact, SHP2 inhibitors appear to be among the best concepts we’ve seen out of the 75+ we’ve tested over the years. These data have already been reviewed by our Medical and Scientific Advisory Boards, who endorsed evaluation of the SHP2 inhibitor concept in chordoma patients. These drugs are available to certain patients today through ongoing SHP2 inhibitor clinical trials (some of which are open to chordoma patients) or compassionate use.

Chordoma patients in need of a systemic therapy option are encouraged to discuss SHP2 inhibitors with their providers. When chordoma patients enroll on SHP2 inhibitor clinical trials, clinical data can be collected that could strengthen the case for future trials to evaluate SHP2 inhibitors in chordoma. (If you’re a patient or caregiver with questions about treatment options, including clinical trials, reach out to our Patient Navigators for personalized support.)

“Chordoma patients urgently need better treatment options once surgery and radiation are no longer appropriate, and we’re thrilled that our long-running partnership with the Chordoma Foundation has resulted in brand new ideas for how to target this disease,” says Stuart Schreiber, PhD, renowned Harvard professor and founding member of the Broad Institute, who led this work along with Broad senior scientist Tanaz Sharifina, PhD. “It will be exciting to explore these findings further and see them translated into better treatment options for patients.”

This paper represents an example of the advances in chordoma research made possible by our Drug Screening Program, through which we can rapidly translate discoveries from bench to bedside. And thanks to Chordoma Foundation Labs, we’re positioned to help our collaborators follow up on new potential therapeutic strategies more quickly than ever.

We’re deeply grateful to all of the donors whose generosity made this work possible, particularly Team Mac and the family of another chordoma patient.