In a groundbreaking advancement for the treatment of soft tissue sarcomas (STS), a consortium of researchers from Singapore’s Agency for Science, Technology and Research (ASTAR), National Cancer Centre Singapore (NCCS), and the National University of Singapore (NUS), in collaboration with biotech innovator KYAN Technologies, has successfully demonstrated the efficacy of a precision medicine platform known as the Quadratic Phenotypic Optimisation Platform (QPOP). Published in the journal npj Precision Oncology* in March 2025, this landmark study offers new hope for patients afflicted with these rare and notoriously stubborn cancers, by enabling highly personalized therapeutic strategies tailored to individual tumor profiles.
Soft tissue sarcomas, comprising a diverse group of malignant tumors originating from connective tissues such as muscle, fat, nerves, and blood vessels, represent less than 1% of global cancer diagnoses. Despite their rarity, STS are disproportionately responsible for a significant fraction of cancers among children and young adults, a demographic that often faces limited treatment options with suboptimal outcomes. The intrinsic heterogeneity of STS poses considerable challenges to conventional chemotherapy protocols, as these tumors frequently demonstrate variable and unpredictable response patterns, underscoring the critical need for more refined, biologically informed treatment approaches.
The QPOP system employed by the research team operates on the principle of functional precision medicine, a cutting-edge methodology that integrates high-throughput, ex vivo phenotypic screening with advanced computational algorithms. This platform evaluates patient-derived tumor cells against a comprehensive panel of approved and investigational drugs, enabling the rapid identification of efficacious drug combinations within a clinically relevant timeframe of approximately seven days. Through this innovative approach, QPOP transcends traditional single-agent testing, harnessing synergy patterns inherent in combinatorial pharmacology to reveal candidate therapies otherwise overlooked in standard clinical practice.
A cohort of 45 primary STS patient tumor samples, the largest such study of ex vivo drug sensitivity to date, was analyzed to validate QPOP’s predictive accuracy. Remarkably, the results demonstrated a greater than 70% concordance between patients’ clinical responses to standard-of-care treatments and their corresponding ex vivo sensitivity profiles determined by QPOP. This finding not only reinforces the platform’s reliability but also introduces a paradigm shift in how therapeutic decisions may be informed, aligning them more closely with the tumor’s intrinsic biological behavior.
Beyond validating existing therapies, QPOP’s real transformative potential emerged when deployed to identify unconventional, personalized drug combinations for patients exhibiting resistance to standard regimens. In select cases, this approach yielded compelling clinical responses, highlighting the capacity of functional precision medicine to uncover novel, patient-specific therapeutic strategies. Such bespoke interventions have profound implications, particularly for complex and treatment-refractory STS cases that have exhausted all conventional options, illuminating a path forward through data-driven innovation.
One of the study’s most significant breakthroughs was the identification of a synergistic drug pairing: AZD5153, a potent inhibitor of the bromodomain-containing protein BRD4, combined with pazopanib, a multi-kinase inhibitor already approved for certain sarcoma subtypes. This novel combination demonstrated superior efficacy over existing treatments across various STS subtypes, both in patient-derived cell lines and in vivo preclinical models. Notably, this regimen effectively suppressed MYC oncogene activity, a notoriously difficult molecular target implicated in the proliferation and survival of numerous cancer types. Inhibition of MYC and associated signaling cascades positions AZD5153-pazopanib as a promising candidate to disrupt core oncogenic drivers in STS pathology.
The capability of QPOP to systematically dissect and exploit molecular vulnerabilities in heterogeneous tumor populations marks a significant leap in oncology therapeutics. By employing high-dimensional phenotypic datasets and advanced quadratic optimization algorithms, the platform can navigate vast combinatorial drug landscapes, rapidly converging on treatment regimens that maximize therapeutic benefit while minimizing toxicity. This precision-guided strategy aligns with the growing trend towards personalized oncology, where the complexity of a patient’s tumor biology directly informs clinical decision-making.
Leading the study, Assistant Professor Valerie Yang emphasized the clinical relevance of these findings, highlighting both the accuracy of ex vivo drug sensitivity testing and the exciting potential of the novel drug combinations discovered. The practical implications of this research extend beyond the laboratory, demonstrating that functional precision medicine platforms can generate actionable insights that translate into tangible patient benefits, even in cancers as challenging as soft tissue sarcomas.
Dr. Tan Boon Toh, head of the Translational Core Laboratory at the National University of Singapore and co-corresponding author, echoed these sentiments, underscoring the pivotal nature of this work in transforming therapeutic paradigms for rare and aggressive cancers. The QPOP platform’s ability to tailor drug combinations to individual tumor phenotypes represents a critical step toward realizing the promise of precision medicine, moving the field closer to a future where treatment efficacy is maximized and adverse effects are reduced.
Looking ahead, the research team acknowledges that these promising preliminary results warrant further validation through prospective clinical trials. Plans are underway in Singapore to initiate such trials to test the broader applicability of QPOP-guided therapies across additional cancer types. The success of these trials could establish functional phenotypic screening as a new standard in precision oncology, catalyzing improved outcomes in cancers traditionally deemed intractable.
The study also underscores the importance of collaborative, multidisciplinary efforts spanning basic research, clinical oncology, computational biology, and biotechnology industries. Contributions from bioinformatics experts at A*STAR’s Bioinformatics Institute were instrumental in the sophisticated data analysis underpinning QPOP, highlighting the synergy between experimental and computational expertise required to navigate complex biological systems effectively.
In summary, this pioneering research embodies the convergence of molecular biology, computational science, and clinical medicine, revealing a viable pathway to optimize cancer treatment in the face of tumor heterogeneity and therapeutic resistance. With the ability to rapidly generate personalized drug combinations that address the unique characteristics of each patient’s cancer, QPOP exemplifies the future of precision medicine—where data-driven, functional assays guide clinical practice, offering hope and extended survival to patients confronting rare and difficult-to-treat malignancies like soft tissue sarcomas.
Subject of Research: Not applicable
Article Title: Functional combinatorial precision medicine for predicting and optimizing soft tissue sarcoma treatments
News Publication Date: 22-Mar-2025
Web References: https://www.nature.com/articles/s41698-025-00851-7
References: Chan, S.P.Y., Rashid, M.B.M.A., Lim, J.J. et al. Functional combinatorial precision medicine for predicting and optimising soft tissue sarcoma treatments. npj Precis. Onc. 9, 83 (2025).
Image Credits: Not specified
Keywords: Clinical medicine
