A new study from The Institute of Cancer Research, London, has revealed significant biological differences in soft tissue sarcomas between adolescent and young adult (AYA) patients (16-39 years) and older adults. This research addresses the long-standing question of why survival improvements in AYA sarcoma patients have lagged behind other age groups. The findings, published in Communications Medicine, identify potential biomarkers to predict aggressive forms of sarcoma in AYA patients, potentially guiding more effective and tailored treatment strategies.
Disparities in Sarcoma Outcomes
Soft tissue sarcomas, rare cancers affecting connective tissues, show a disproportionately lower survival rate improvement in AYA patients compared to pediatric and older adult populations. Researchers analyzed protein profiles from 309 patients with soft tissue sarcomas and benign desmoid tumors, identifying 8,148 proteins and quantifying 3,299. The study revealed 32 proteins more abundant in AYA patients and 35 more abundant in older adults. After adjusting for variables like tumor size and sarcoma subtype, five proteins remained significant, highlighting age-related biological distinctions.
Key Protein Differences and Clinical Implications
Older patients exhibited higher levels of a protein regulating the cell cycle, while AYA patients showed increased abundance of proteins involved in structural support and mitochondrial function. These differences may influence how sarcomas respond to treatment and impact survival rates. High expression of specific splicing subunits was associated with better metastasis-free survival (MFS) in AYA patients, suggesting a potential biomarker for identifying patients at higher risk of cancer spread.
Splicing Signature as a Predictive Tool
The identified splicing signature could help clinicians determine which AYA patients require more intensive treatment to prevent metastasis. This approach aims to improve outcomes for high-risk patients while sparing those with less aggressive cancers from unnecessary overtreatment and associated side effects.
Future Directions and Expert Perspectives
Yuen Bun Tam, a PhD student at the ICR and first author of the study, emphasized the unmet need for therapies tailored to AYA patients. "By demonstrating the importance of age-specific studies in the discovery of more tailored strategies, such as targeted agents, we hope that our findings will encourage future studies and clinical trials to include more adolescents and young adults. In the long term, this could lead to substantial improvements in survivorship and the management of late effects for this age group."
Dr. Paul Huang, Leader of the Molecular and Systems Oncology Group at the ICR and senior author, noted the surprising independence of these biological differences from other clinical factors. "We are planning further work to validate our findings in larger cohorts and to measure our splicing signature, with the hope of making it feasible to use as a clinical test. We will also work on better understanding the link between this splicing signature and the ability of the tumour to spread. This knowledge could aid the identification of new treatment options to manage soft tissue tumours in adolescents and young adults."
