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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Precision Medicine for the Management of Therapy Refractory Colorectal Cancer
Hossein Taghizadeh1,2, Robert M Mader1,2, Leonhard Müllauer2,3
1Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, 1090 Vienna, Austria.
Abstract:
In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the molecular profiles of 60 mCRC patients. Tumor samples of the patients were analyzed using next-generation sequencing panels of mutation hotspots, microsatellite instability testing, and immunohistochemistry. All profiles were reviewed by a multidisciplinary team to provide a targeted treatment recommendation after consensus discussion. In total, we detected 166 mutations in 53 patients. The five most frequently found mutations were TP53, KRAS, APC, PIK3CA, and PTEN. In 28 cases (47% of all patients), a molecularly targeted therapy could be recommended. Eventually, 12 patients (20%) received the recommended therapy. Six patients (10%) had a clinical benefit. The median time to treatment failure was 3.1 months. Our study demonstrates the feasibility and applicability of using targeted therapies in daily clinical practice for heavily pretreated mCRC patients. This could be used as a targeted treatment option in half of the patients.
Insights
Molecularly targeted therapies show feasibility for metastatic colorectal cancer (mCRC) patients. A significant portion could receive targeted treatments, with some experiencing clinical benefit.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Metastatic colorectal cancer (mCRC) patients often exhaust standard treatments.
- Identifying effective therapies for heavily pretreated mCRC is crucial.
Purpose of the Study:
- To evaluate the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated mCRC.
- To assess the utility of a precision medicine platform for treatment recommendations.
Main Methods:
- Retrospective analysis of 60 mCRC patients.
- Next-generation sequencing (NGS) panels, microsatellite instability (MSI) testing, and immunohistochemistry (IHC) for molecular profiling.
- Multidisciplinary team review for targeted therapy recommendations.
Main Results:
- 166 mutations detected in 53 patients; TP53, KRAS, APC, PIK3CA, and PTEN were most frequent.
- Targeted therapy recommended for 47% (28/60) of patients.
- 20% (12/60) received recommended therapy, with 10% (6/60) showing clinical benefit.
Conclusions:
- Molecular profiling and targeted therapies are feasible in clinical practice for heavily pretreated mCRC.
- Approximately half of mCRC patients may be candidates for targeted treatment options.
- Further investigation into optimizing targeted therapy selection and outcomes is warranted.
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