We’re happy to share that our research team has recently identified two potential new therapeutic options for chordoma patients: One is gemcitabine, a widely-used, low-cost cancer drug, and the other is a class of drugs called ATR inhibitors, which are currently in clinical development.
Both of these concepts exploit a phenomenon called replication stress, which appears to be prevalent in chordoma. Replication stress occurs when DNA in a cell is being copied, or replicated, and encounters a “stress” that can compromise this process and lead to DNA damage. Hints for the replication stress hypothesis in chordoma came from researchers at the National Center for Tumor Diseases in Germany; our grantees and collaborators at the Broad Institute of MIT and Harvard; and a member of our Medical Advisory Board (MAB), Greg Cote, MD, PhD, of Massachusetts General Hospital.
Through Chordoma Foundation Labs and our Drug Screening Program we were able to quickly generate data in chordoma cells and mouse models. Our results show that in mice, in many cases gemcitabine and ATR inhibitors are indeed effective at slowing chordoma tumor growth or even — in some cases — causing the tumors to disappear entirely. In fact, gemcitabine induced the most significant shrinkage of chordoma tumors among the more than 80 drugs we’ve tested to date. As a result of this compelling data, our MAB recently endorsed both of these concepts for clinical testing.
Because gemcitabine is already approved for other cancers, chordoma patients in need of systemic therapy and their oncologists could consider it as an off-label option. (Contact your doctor or a Patient Navigator with questions about drug therapy options. And if you’re a patient who’s been prescribed gemcitabine, we’d love to hear how it’s going.)
Though ATR inhibitors are not yet FDA approved for any tumor type, several are currently in clinical trials and we’re now working to create opportunities for chordoma patients to participate in such a trial — either by expanding an existing trial to include chordoma patients or opening a new trial specifically for chordoma.
Both of these concepts will undergo further preclinical testing in Chordoma Foundation Labs to determine which patients might be most likely to benefit, and whether combination therapies could maximize the effectiveness of this approach.
Replication stress is an evolving story in chordoma. In a poster at the annual meeting of the American Association of Cancer Research (AACR) this week, we shared what we've learned about it so far, including our mechanistic and preclinical rationale for exploiting it therapeutically. We’re exploring the hypothesis further in collaboration with Dr. Cote and Lee Zou, PhD, a DNA replication expert at Duke University School of Medicine.
We’re grateful to donors to Chordoma Foundation Labs and our Drug Screening Program for enabling these new findings, and for supporting our growing pipeline of promising therapeutic concepts which are advancing to the clinic more rapidly than ever.