A groundbreaking study led by researchers from A*STAR, the National Cancer Centre Singapore (NCCS), and the National University of Singapore (NUS), in collaboration with biotech firm KYAN Technologies, has revealed significant advancements in treating soft tissue sarcomas (STS) using precision medicine. Published in npj Precision Oncology in March 2025, this research highlights the potential of data-driven phenotypic screening to improve treatment selection for STS patients. The study addresses the challenges posed by these rare and complex tumors, which account for less than 1% of all cancers globally but disproportionately affect younger populations. By employing a platform called QPOP, the team demonstrated its ability to predict drug sensitivity and identify unconventional treatment combinations, offering hope for improved patient outcomes.

Soft tissue sarcomas are notoriously difficult to treat due to their heterogeneity and rarity, making large-scale clinical trials impractical. To address this, researchers turned to precision medicine, analyzing individual tumor characteristics to tailor treatments. At the heart of the study was the Quadratic Phenotypic Optimization Platform (QPOP), a tool that uses phenotypic screening to identify effective drug combinations within seven days. The team screened tumor samples from 45 primary STS patients, representing the largest ex vivo drug testing cohort reported to date. Results indicated that over 70% of patient responses aligned with predictions made by QPOP, confirming its accuracy and reliability.

In addition to validating QPOP's predictive capabilities, the study explored its potential to uncover personalized drug combinations for patients unresponsive to standard therapies. Two such cases were highlighted, where alternative treatments identified through QPOP yielded compelling clinical responses. This application underscores the promise of functional precision medicine in devising novel strategies for complex and resistant cancers.

The researchers also used QPOP to discover new treatment combinations. Notably, they found that combining AZD5153, a BRD4 inhibitor, with pazopanib, a multi-kinase blocker, outperformed standard treatments across multiple STS subtypes. Laboratory experiments in patient-derived cell lines and in vivo models confirmed the effectiveness of this combination, which suppresses MYC, an oncogene notoriously challenging to target, and related pathways crucial in various cancers.

Assistant Professor Valerie Yang, who spearheaded the study, emphasized its transformative potential. "Our findings demonstrate that ex vivo drug testing can accurately predict patient responses while providing valuable insights into managing refractory cases," she stated. Co-corresponding authors Dr. Tan Boon Toh and Dr. Edward Kai-Hua Chow further noted the importance of advancing precision medicine for rare and aggressive cancers like STS.

This research represents a critical milestone in cancer treatment. By leveraging QPOP to match patients with optimized drug regimens based on their tumor biology, it brings us closer to realizing the full potential of functional precision medicine. While additional clinical trials are necessary to validate these findings and expand QPOP's applicability to other cancer types, the initial results are promising. The team is currently planning a prospective clinical trial in Singapore to build on these achievements.