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Response to anti-DKK1 therapy in uterine carcinosarcoma: A case report
A ElNaggar1, N Zhang2, C B Scalise3
1Division of Gynecologic Oncology, West Cancer Center and Research Institute, Memphis, TN, USA.
Abstract:
Targeted therapies are being increasingly used in clinical practice and trials. However, tumor heterogeneity among sites of metastatic disease can occur creating a conundrum when utilizing biomarker directed therapies. Here we demonstrate a patient with recurrent uterine carcinosarcoma whose local recurrence and metastatic recurrence had a varied response to paclitaxel in combination with DKN-01, a monoclonal antibody against DKK1, a modulator of Wnt/β-catenin and PI3K/AKT signaling pathways. This may be explained by differences in mutational profile found between the two sites. Our findings highlight the importance of analyzing tissue from the primary tumor as well as metastatic lesions, especially if there is a discrepancy in their response to treatment.
Insights
Tumor heterogeneity can impact targeted therapy effectiveness. Analyzing both primary and metastatic tumor mutations is crucial for personalized uterine carcinosarcoma treatment, especially when responses vary.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapies and biomarker-directed treatments are increasingly vital in clinical oncology.
- Tumor heterogeneity across metastatic sites presents challenges for personalized treatment strategies.
- Understanding molecular differences between primary and metastatic lesions is key.
Observation:
- A patient with recurrent uterine carcinosarcoma exhibited differential responses to paclitaxel and DKN-01 (anti-DKK1 antibody).
- Local recurrence responded differently to therapy compared to metastatic recurrence.
- DKK1 modulates Wnt/β-catenin and PI3K/AKT signaling pathways, relevant in cancer progression.
Findings:
- Varied therapeutic response correlated with distinct mutational profiles between local and metastatic tumor sites.
- Differences in genomic alterations may explain the observed discrepancy in treatment efficacy.
- Paclitaxel in combination with DKN-01 showed site-specific effectiveness.
Implications:
- Highlights the necessity of comprehensive genomic profiling of both primary and metastatic tumors.
- Emphasizes the importance of re-biopsy and molecular analysis when treatment response is inconsistent.
- Informs personalized treatment selection for uterine carcinosarcoma by accounting for tumor heterogeneity.
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