Hope for Osteosarcoma: New Subtypes Discovered, Paving the Way for Targeted Treatments
A groundbreaking discovery offers new hope in the fight against osteosarcoma, a rare and aggressive bone cancer primarily affecting children and teens. Researchers have identified at least three distinct subtypes of this cancer, a finding that could revolutionize clinical trials and dramatically improve patient outcomes.While genetic sequencing has successfully categorized subtypes in other cancers like breast and skin cancer, osteosarcoma has proven substantially more challenging.
A team from the university of east anglia, supported by Children with Cancer UK, employed advanced mathematical modeling and machine learning—a technique called Latent Process Decomposition (LPD)—to analyze genetic data from osteosarcoma patients. This innovative approach allowed them to classify patients into distinct subgroups based on their unique genetic profiles. Previously, all patients received the same treatment protocols, leading to widely varying results.
A Paradigm Shift in Osteosarcoma Treatment
for decades, osteosarcoma treatment has relied on non-targeted chemotherapy and surgery, sometimes resulting in limb amputations and severe long-term side effects from chemotherapy. Dr. Darrell Green, lead author of the study, explains that despite numerous international clinical trials exploring new drugs, many have been deemed “failed” over the past 50 years.
Though, this new research reveals a crucial detail: even in these seemingly unsuccessful trials, a small percentage of patients (5-10%) responded positively to the new drugs. This suggests the existence of osteosarcoma subtypes that are indeed responsive to these treatments. The drugs weren’t entirely ineffective; they simply weren’t effective for *all* patients,highlighting the need for a more targeted approach.
The researchers are optimistic that this new algorithm, by grouping patients according to their subtype, will finally lead to successful clinical trials—a milestone that has eluded researchers for over half a century. The ability to administer targeted medications specific to each subtype promises a significant departure from the current reliance on broad-spectrum chemotherapy.
This research is a key focus for Children with Cancer UK, which funded the UEA team’s work in 2021. Dr. Sultana Choudhry, head of research at the charity, emphasizes the importance of this breakthrough, stating, “investing in pioneering research programs is essential to advancing our vision of a world where every child and young person survives cancer.”
While the osteosarcoma survival rate has remained stagnant at around 50% for 45 years,this subtype identification represents a major step forward. A lack of understanding regarding osteosarcoma subtypes and the tumor’s interaction with the immune system has hampered progress.The inability to identify key biological markers to predict patient prognosis or treatment response has further hindered advancements in survival rates.
Previous computational methods for predicting osteosarcoma types failed to account for the variability within individual tumors. The LPD method, however, addresses this limitation by analyzing the tumor as a complex mixture of gene activity patterns, each representing a distinct “functional state.” Although the study had limitations, including a relatively small dataset for LPD model development and incomplete clinical information in the validation group, the method reliably identified consistent osteosarcoma subgroups across four autonomous datasets. Future improvements in data collection are expected to further refine the LPD model and uncover even more specific subtypes.
This significant research has been published in Briefings in Bioinformatics, offering a beacon of hope for families affected by this devastating disease and underscoring the critical need for continued investment in pediatric cancer research.
