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Article: Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105

TitleModulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105
Authors
Keywordsblood
female
human
maleneoplasm
pathology
Issue Date2018
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/
Citation
Molecular Cancer Therapeutics, 2018, v. 17 n. 10, p. 2248-2256 How to Cite?
AbstractTRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy. Upon treatment with BEV and TRC105, pharmacodynamic changes in response to both BEV (PlGF increase) and TRC105 (soluble endoglin increase) were noted. In addition, distinct patterns of change were identified (similar, opposing, neutralizing). Similar patterns were observed when the combination elicited similar effects to those observed with monotherapy treatment (i.e., decreases of Ang-2, increases of IL6 and VCAM-1). Opposing patterns were observed when the combination led to opposing effects compared with monotherapy treatment (i.e., TGFβ1, PDGF-AA and PDGF-BB, PAI-1). Lastly, neutralizing patterns were observed when one drug led to increase, whereas the other drug led to decrease, and the combination elicited no overall effect on the marker (i.e., VEGF-A, VEGF-D, and IGFBP-3). Patients achieving partial responses or stable disease from the combination exhibited significantly lower expression of E-Cadherin, HGF, ICAM-1, and TSP-2 at baseline. Taken together, the novel biomarker modulations identified may deepen our understanding of the underlying biology in patients treated with BEV and TRC105 compared with either drug alone. Mol Cancer Ther; 17(10); 2248–56. ©2018 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/274530
ISSN
2023 Impact Factor: 5.3
2023 SCImago Journal Rankings: 2.270
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Y-
dc.contributor.authorStarr, MD-
dc.contributor.authorBrady, JC-
dc.contributor.authorRushing, C-
dc.contributor.authorPang, H-
dc.contributor.authorAdams, B-
dc.contributor.authorAlvarez, D-
dc.contributor.authorTheuer, CP-
dc.contributor.authorHurwitz, HI-
dc.contributor.authorNixon, AB-
dc.date.accessioned2019-08-18T15:03:32Z-
dc.date.available2019-08-18T15:03:32Z-
dc.date.issued2018-
dc.identifier.citationMolecular Cancer Therapeutics, 2018, v. 17 n. 10, p. 2248-2256-
dc.identifier.issn1535-7163-
dc.identifier.urihttp://hdl.handle.net/10722/274530-
dc.description.abstractTRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy. Upon treatment with BEV and TRC105, pharmacodynamic changes in response to both BEV (PlGF increase) and TRC105 (soluble endoglin increase) were noted. In addition, distinct patterns of change were identified (similar, opposing, neutralizing). Similar patterns were observed when the combination elicited similar effects to those observed with monotherapy treatment (i.e., decreases of Ang-2, increases of IL6 and VCAM-1). Opposing patterns were observed when the combination led to opposing effects compared with monotherapy treatment (i.e., TGFβ1, PDGF-AA and PDGF-BB, PAI-1). Lastly, neutralizing patterns were observed when one drug led to increase, whereas the other drug led to decrease, and the combination elicited no overall effect on the marker (i.e., VEGF-A, VEGF-D, and IGFBP-3). Patients achieving partial responses or stable disease from the combination exhibited significantly lower expression of E-Cadherin, HGF, ICAM-1, and TSP-2 at baseline. Taken together, the novel biomarker modulations identified may deepen our understanding of the underlying biology in patients treated with BEV and TRC105 compared with either drug alone. Mol Cancer Ther; 17(10); 2248–56. ©2018 AACR.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/-
dc.relation.ispartofMolecular Cancer Therapeutics-
dc.subjectblood-
dc.subjectfemale-
dc.subjecthuman-
dc.subjectmaleneoplasm-
dc.subjectpathology-
dc.titleModulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105-
dc.typeArticle-
dc.identifier.emailPang, H: herbpang@hku.hk-
dc.identifier.authorityPang, H=rp01857-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1535-7163.MCT-17-0916-
dc.identifier.pmid29997150-
dc.identifier.scopuseid_2-s2.0-85054070678-
dc.identifier.volume17-
dc.identifier.issue10-
dc.identifier.spage2248-
dc.identifier.epage2256-
dc.identifier.isiWOS:000456145700017-
dc.publisher.placeUnited States-
dc.identifier.issnl1535-7163-

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