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Biomarkers of response and resistance to antiangiogenic therapy
Rakesh K Jain1, Dan G Duda, Christopher G Willett
1Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA. jain@steele.mgh.harvard.edu
Abstract:
No validated biological markers (or biomarkers) currently exist for appropriately selecting patients with cancer for antiangiogenic therapy. Nor are there biomarkers identifying escape pathways that should be targeted after tumors develop resistance to a given antiangiogenic agent. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged from recently completed phase I-III studies. Some of these are measured at baseline (for example VEGF polymorphisms), others are measured during treatment (such as hypertension, MRI-measured K(trans), circulating angiogenic molecules or collagen IV), and all are mechanistically based. Some of these biomarkers might be pharmacodynamic (for example, increase in circulating VEGF, placental growth factor) while others have potential for predicting clinical benefit or identifying the escape pathways (for example, stromal-cell-derived factor 1alpha, interleukin-6). Most biomarkers are disease and/or agent specific and all of them need to be validated prospectively. We discuss the current challenges in establishing biomarkers of antiangiogenic therapy, define systemic, circulating, tissue and imaging biomarkers and their advantages and disadvantages, and comment on the future opportunities for validating biomarkers of antiangiogenic therapy.
Insights
Validated biomarkers are needed for selecting cancer patients for antiangiogenic therapy and identifying resistance pathways. Current research explores various systemic, circulating, tissue, and imaging biomarkers for improved treatment selection and monitoring.
Area of Science:
- Oncology
- Pharmacology
- Biomarker Discovery
Background:
- No validated biomarkers currently exist for selecting cancer patients for antiangiogenic therapy.
- There is a lack of biomarkers to identify tumor resistance pathways to antiangiogenic agents.
Purpose of the Study:
- To discuss challenges in establishing biomarkers for antiangiogenic therapy.
- To define different types of biomarkers (systemic, circulating, tissue, imaging) and their pros and cons.
- To explore future opportunities for validating antiangiogenic therapy biomarkers.
Main Methods:
- Review of potential biomarkers from Phase I-III studies.
- Categorization of biomarkers based on measurement time (baseline, during treatment).
- Discussion of mechanistic basis and potential applications (pharmacodynamic, predictive, resistance identification).
Main Results:
- Several potential biomarkers have emerged, including VEGF polymorphisms, hypertension, MRI-measured K(trans), and circulating angiogenic molecules.
- Some biomarkers are pharmacodynamic (e.g., VEGF, placental growth factor), while others may predict clinical benefit or identify escape pathways (e.g., SDF-1alpha, IL-6).
- Most biomarkers are disease and/or agent specific and require prospective validation.
Conclusions:
- Establishing reliable biomarkers for antiangiogenic therapy is challenging.
- Diverse biomarkers show promise but need rigorous validation.
- Future research should focus on prospective validation of these biomarkers for clinical utility.
