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ABSTRACT Pericytes are crucial for angiogenesis. The impact of pericyte function to bevacizumab efficacy in mCRC treatment has not been comprehensively examined. This retrospective study

investigated germline polymorphisms in genes related to early pericyte maturation to predict bevacizumab efficacy in 424 patients of two clinical trials treated first line with

FOLFIRI+bevacizumab. Eight single-nucleotide polymorphisms (SNPs) were tested for potential biomarker value: RGS5 (regulator of G-protein signaling 5; rs1056515, rs2661280), PDGFR-β

(platelet-derived growth factor receptor-β; rs2229562, rs2302273), CSPG4 (chondroitin sulfate proteoglycan NG2; rs8023621, rs1127648) and RALBP1 (RalA binding protein 1; rs10989, rs329007).

For progression-free survival (PFS), PDGFR-β (rs2302273) was able to define significantly different patient cohorts in uni- and multivariate testing. RALPB1 (rs329007) showed predictive

value for tumor response. The C allele in RGS5 (rs2661280) predicted longer overall survival and CSPG4 rs1127648 was associated with differences in PFS, but for both value was lost when

multivariate analysis was applied. A comprehensive statistical analysis revealed that the biomarker value of the SNPs was dependent on primary tumor location. This is the first study to

identify pericyte germline polymorphisms associated with clinical outcome in mCRC patients treated first line with FOLFIRI+bevacizumab. The differences seen with regard to primary tumor

location may lead to further research to understand the clinical outcome differences seen in right- and left-sided colon cancer. Access through your institution Buy or subscribe This is a

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VALIDATION OF _VEGF_ AND _ENOS_ POLYMORPHISMS AS PREDICTORS OF FIRST-LINE BEVACIZUMAB EFFICACY IN PATIENTS WITH METASTATIC COLORECTAL CANCER Article Open access 09 August 2023 _VEGF-A_,

_VEGFR1_ AND _VEGFR2_ SINGLE NUCLEOTIDE POLYMORPHISMS AND OUTCOMES FROM THE AGITG MAX TRIAL OF CAPECITABINE, BEVACIZUMAB AND MITOMYCIN C IN METASTATIC COLORECTAL CANCER Article Open access

24 January 2022 CLINICAL SIGNIFICANCE OF ENTEROCYTE-SPECIFIC GENE POLYMORPHISMS AS CANDIDATE MARKERS OF OXALIPLATIN-BASED TREATMENT FOR METASTATIC COLORECTAL CANCER Article 04 February 2021

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ACKNOWLEDGEMENTS This study was supported by the NIH Grant 5 P30CA14089-27S1 and Nancy Bernstein Call to Cure Foundation. SS is granted a postdoctoral fellowship by the German Cancer Aid

(Mildred-Scheel-Foundation). AUTHOR INFORMATION Author notes * N B Volz and S Stintzing: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * USC/Norris Comprehensive

Cancer Center, Keck School of Medicine, Sharon Carpenter Laboratory, Los Angeles, CA, USA N B Volz, S Stintzing, W Zhang, Y Ning, T Wakatsuki, R E El-Khoueiry, J E Li, A Kardosh & H-J

Lenz * Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA D Yang & H-J Lenz * Department of Gastroenterology Center,

Cancer Institute Hospital, Tokyo, Japan T Wakatsuki * UO Oncologia Medica 2 – Aziendo Ospedaliero-Universitaria Pisana, Pisa, Italy F Loupakis, C Cremolini & A Falcone * University of

Wuerzburg, Biocenter Physiological Chemistry, Wuerzburg, Germany S J Scherer Authors * N B Volz View author publications You can also search for this author inPubMed Google Scholar * S

Stintzing View author publications You can also search for this author inPubMed Google Scholar * W Zhang View author publications You can also search for this author inPubMed Google Scholar

* D Yang View author publications You can also search for this author inPubMed Google Scholar * Y Ning View author publications You can also search for this author inPubMed Google Scholar *

T Wakatsuki View author publications You can also search for this author inPubMed Google Scholar * R E El-Khoueiry View author publications You can also search for this author inPubMed 

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 Google Scholar * F Loupakis View author publications You can also search for this author inPubMed Google Scholar * C Cremolini View author publications You can also search for this author

inPubMed Google Scholar * A Falcone View author publications You can also search for this author inPubMed Google Scholar * S J Scherer View author publications You can also search for this

author inPubMed Google Scholar * H-J Lenz View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to H-J Lenz. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Volz, N., Stintzing, S., Zhang, W. _et al._ Genes involved in pericyte-driven tumor maturation predict treatment benefit of first-line

FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer. _Pharmacogenomics J_ 15, 69–76 (2015). https://doi.org/10.1038/tpj.2014.40 Download citation * Received: 11 February

2014 * Revised: 13 May 2014 * Accepted: 04 June 2014 * Published: 29 July 2014 * Issue Date: February 2015 * DOI: https://doi.org/10.1038/tpj.2014.40 SHARE THIS ARTICLE Anyone you share the

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