Value Proposition
· Improved Prognostic Accuracy: Dual detection of RASAL1 and PTEN alterations enables highly accurate identification of aggressive cancers and risk stratification. These biomarkers provide greater precision in identifying aggressive cancers compared to established markers, enabling better patient management.
· Pan-Cancer Relevance: Concurrent alterations in RASAL1 and PTEN were found in 33 types of human cancer. This includes many common solid tumors and certain hematologic malignancies. The technology offers broad clinical utility and is relevant for a wide spectrum of cancer patients.
· Enables Precision Oncology: Allows oncologists and care teams to better risk-stratify patients for treatment selection, surveillance, and clinical trial. This improved precision helps minimize both overtreatment and undertreatment.
· Seamless Clinical Integration: Can be implemented using routine diagnostic technologies such as PCR or next-generation sequencing. This technology is flexible enough for use as a standalone test or as part of new, multi-gene diagnostic kits in clinical laboratories.
· Strong Mechanistic and Regulatory Basis: This technology is backed by extensive patient data and validated in mouse studies. It links co-alteration of RASAL1 and PTEN to overactive PI3K-AKT signaling and poor clinical outcomes, providing a robust foundation for research, regulatory approval, and new targeted therapies.
Unmet Need
· Many cancers remain difficult to predict in terms of aggressive behavior and patient outcome, leading to missed curative opportunities or unnecessary treatment burden.
· The standard of care currently relies on traditional biomarkers like TP53 or broad multi-gene panels, which do not account for the combined effect of RASAL1 and PTEN alterations.
· Current approaches often fail to identify high-risk patients and cannot fully support precision medicine strategies.
· There is no existing diagnostic platform that detects the powerful synergistic impact of RASAL1 and PTEN alterations in routine clinical practice.
· Therefore, there is a strong need for detection of RASAL1 and PTEN alteration status together, allowing for more accurate risk assessment, better-directed therapies, and improved patient survival.
Technology Description
Researchers have identified that concurrent genetic alterations in tumor suppressor genes RASAL1 and PTEN serve as strong prognostic biomarkers for cancer aggressiveness across multiple cancer types. This approach focuses on detecting concurrent alterations in the RASAL1 and PTEN genes, with optional inclusion of TP53, in patient samples. Analysis of nearly 10,000 patient samples and advanced mouse models revealed that RASAL1 is frequently altered genetically in human cancers, with over half also carrying concurrent mutations in PTEN. These combined loss-of-function alterations synergistically activate the PI3K-AKT pathway, driving tumor progression, metastasis, therapy resistance, and increased mortality. This approach, which detects RASAL1 and PTEN alterations (with optional TP53 inclusion), reveals tumor suppressor cooperation missed by standard genetic panels, offering improved accuracy for precision cancer care. This genetic mechanism represents a novel prognostic framework that could be integrated into molecular-based clinical risk stratification for personalized cancer management.
Data Availability: Data available upon request.
Publications: Mol Oncol. . 2025 Jan;19(1):248-259. doi: 10.1002/1878-0261.13701
