Researchers have found that the gene SERPINE1 spikes sharply in tumor tissue after patients with advanced soft tissue sarcoma (STS) take the drug pazopanib (Votrient). The increase appears earliest in the most drug-sensitive sarcoma cell lines, suggesting this marker could serve as a real-time signal of treatment success.
Soft tissue sarcoma is a rare and heterogeneous cancer group that leaves patients with few options once first-line therapy ends. Second-line treatments like pazopanib, gemcitabine, eribulin, and trabectedin generally produce response rates below 10% and a median progression-free survival of just 4 to 5 months. Even the key phase 3 PALETTE trial, which established pazopanib’s role, failed to identify a reliable predictive biomarker.
The study, published in Therapeutic Advances in Medical Oncology, adds SERPINE1 to a very short list of candidate biomarkers for the disease. Pazopanib is an oral tyrosine kinase inhibitor that targets receptors overexpressed in STS, which are linked to worse prognosis, metastatic disease, and resistance to chemotherapy.
The Data Behind the Discovery
Researchers analyzed paired tumor samples from 11 patients before and after pazopanib treatment, using a 549-gene panel. Of the 38 genes that changed after treatment, only four survived statistical corrections. Among these, SERPINE1 showed the largest change, with a 4.19-fold increase in expression. The gene encodes plasminogen activator inhibitor-1 (PAI-1), a regulator of fibrinolysis and angiogenic signaling.
In a separate analysis of the Cancer Genome Atlas sarcoma database, higher SERPINE1 levels were associated with worse progression-free and disease-free survival, though not overall survival. Follow-up experiments on sarcoma cell lines confirmed that expression rises after pazopanib treatment and appears earlier in the drug-sensitive lines than in the resistant ones.
This approach offers a different signal than traditional biomarkers. While markers like PD-L1, microsatellite instability, and tumor mutation burden have shown limited value in sarcomas, SERPINE1 is a direct change in tumor tissue triggered by the drug. The goal is to match patients to therapies that will work and spare others weeks of toxicity without benefit.
The findings are exploratory and limited by the small sample size and the different prior treatments the patients had received. The authors noted that SERPINE1’s value as a predictive marker remains an indirect finding. They suggested testing whether these changes can be detected in liquid biopsies to flag responders within 24 to 72 hours. A large-scale, prospective validation in uniformly treated patient cohorts is strictly required before any clinical application can be considered.
Pazopanib works by blocking the signals that allow cancer cells to grow and spread, though it is not effective for every patient. To better identify who will respond, scientists are looking at how specific genes react to the medication. A recent study focused on the gene SERPINE1, which showed a sharp rise in expression after treatment. This increase appears first in the most sensitive sarcoma cell lines, suggesting it could serve as an early indicator of success. The search for reliable biomarkers is critical because current therapies often fail to stop disease progression. Researchers analyzed paired tumor samples from 11 patients and found that SERPINE1 had the largest change among 38 genes that reacted to the drug. The gene encodes plasminogen activator inhibitor-1 (PAI-1), a regulator of fibrinolysis and angiogenic signaling. In the Cancer Genome Atlas sarcoma database, higher SERPINE1 levels were associated with worse progression-free and disease-free survival, though not overall survival.
