Professor Paul Workman, a seasoned medical researcher, is on an ambitious quest against chordoma, a rare bone cancer that claimed his mother's life. His journey is driven by a deeply personal connection, as his mother, Ena, succumbed to the disease after suffering severe back pain that complicated her diagnosis. Chordoma affects approximately one in a million people and remains untreatable. Workman's father had previously died of bowel cancer, adding a layer of urgency to his research. Despite facing his own battle with prostate cancer in 2022, Workman has emerged determined, successfully treated with radiotherapy, and focused on developing a treatment for chordoma.
Chordoma is a rare cancer that presents unique challenges due to its rarity and complexity. Professor Workman's team has pioneered a novel approach using crystallographic fragment screening to identify drug-binding sites on the brachyury protein, which plays a crucial role in chordoma's development.
“Brachyury plays a role in the embryo in promoting the notochord, a precursor of the spine,” Workman explains.
This protein is typically switched off after birth but can reappear in rare cases, triggering chordoma as it did with Ena.
“My father died first, of bowel cancer, many years before my mother succumbed to chordoma,” Workman reflects, highlighting the personal motivation behind his research.
His team utilized the Diamond Light Source synchrotron in Oxfordshire to study the brachyury protein in detail. This cutting-edge facility has allowed them to identify several promising compounds capable of targeting the protein.
“It has allowed us to develop the best-fitting drugs that can fasten on to the protein’s surface,” Workman notes.
The ultimate goal of Workman's research is to develop a treatment that can effectively destroy the brachyury protein, halting the growth of chordoma. The path to achieving this involves rigorous testing, starting with trials in chordoma cell lines and progressing to animal models. This process could take up to five years before human trials begin.
“We need to begin trials in chordoma cell lines first and then in chordoma models in animals before we start trials in humans. That could take five years to complete. Then, hopefully, we will finally be ready to tackle the challenge of chordoma,” Workman states.
This endeavor is not without its challenges. Chordoma's rarity means that there is limited understanding of the disease, and historically, no drugs were available to treat it.
“Thirty-six years ago, there was little we could do to treat chordoma. There was little understanding of the disease and no drugs were available to help my mother,” Workman recalls.
Despite these obstacles, Workman's determination remains steadfast.
“It is thrilling to realise that I am now helping to do something about a disease that killed my mother. It has taken considerable effort by a lot of scientists from centres on both sides of the Atlantic but it has been worth it,” he says.
Beyond chordoma, Workman believes that the techniques being developed could have broader implications for cancer treatment.
“For a start, brachyury appears to be involved in the metastatic spread of other tumours, which means that drugs that block its activities could also help to obstruct the spread of other cancers,” he explains.