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Endoglin Targeting: Lessons Learned and Questions That Remain
Yingmiao Liu1, Madelon Paauwe2, Andrew B Nixon1
1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Abstract:
Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.
Insights
Endoglin, a key factor in tumor angiogenesis, was targeted by the antibody TRC105. Clinical trials revealed new insights into endoglin
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- Endoglin (CD105) functions as a transforming growth factor-beta (TGF-β) coreceptor, vital in development and tumor angiogenesis.
- High endoglin expression on tumor vasculature correlates with poor patient survival, identifying it as a potential cancer therapeutic target.
Purpose of the Study:
- To review preclinical data, clinical trials, and biomarker studies of the endoglin-neutralizing antibody TRC105 (Carotuximab).
- To elucidate the role of endoglin in angiogenesis and its function within the tumor microenvironment.
- To assess the therapeutic potential of targeting endoglin in cancer treatment.
Main Methods:
- Comprehensive review of preclinical cancer models evaluating TRC105 efficacy.
- Analysis of Phase I-III clinical trial data for TRC105 as monotherapy and in combination regimens.
- Examination of biomarker studies to understand endoglin expression and function.
Main Results:
- TRC105 demonstrated activity in various preclinical cancer models.
- Clinical studies provided insights into TRC105's safety, efficacy, and optimal use in combination therapies.
- New understanding of endoglin's broader role in the tumor microenvironment beyond angiogenesis.
Conclusions:
- TRC105 (Carotuximab) represents a promising therapeutic strategy targeting endoglin in cancer.
- Further research is needed to fully understand endoglin's multifaceted roles and optimize TRC105 treatment strategies.
- Biomarker studies are crucial for patient selection and predicting response to endoglin-targeted therapies.
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