Evidence map›Paper›PMID 36816347›Full record

ArticleEClinicalMedicine2023

Impact of genetic variants involved in the lipid metabolism pathway on progression free survival in patients receiving bevacizumab-based chemotherapy in metastatic colorectal cancer: a retrospective analysis of FIRE-3 and MAVERICC trials.

Jingyuan Wang, Joshua Millstein, Yan Yang, Sebastian Stintzing, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Shivani Soni, Wu Zhang, Christoph Mancao and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 4 countries.

Jingyuan WangDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, 200032, China.
Joshua MillsteinDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Yan YangDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Sebastian StintzingDepartment of Hematology, Oncology and Cancer Immunology (CCM), Charité- Universitaetsmedizin Berlin, Germany.
Hiroyuki AraiDivision of Medical Oncology, Norris Comprehensive Cancer Centre, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Francesca BattaglinDivision of Medical Oncology, Norris Comprehensive Cancer Centre, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Natsuko KawanishiDivision of Medical Oncology, Norris Comprehensive Cancer Centre, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shivani SoniDivision of Medical Oncology, Norris Comprehensive Cancer Centre, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wu ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Centre, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Christoph MancaoOncology Biomarker Development, Genentech Inc., Basel, Switzerland.
Chiara CremoliniDepartment of Translational Medicine, University of Pisa, Italy.
Tianshu LiuDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, 200032, China.
Volker HeinemannDepartment of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Alfredo FalconeDepartment of Translational Medicine, University of Pisa, Italy.
Lin ShenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Centre, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
University of Southern California · USFudan University · CNUniversity of Pisa · ITCharité - Universitätsmedizin Berlin · DELudwig-Maximilians-Universität München · DEPeking University · CN

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches glucose-dependent to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer (CRC). Therefore, we hypothesised that genetic variants in the lipid metabolism pathway may predict clinical outcomes [overall response rate (ORR), overall survival (OS) and progression-free survival (PFS)] in metastatic CRC (mCRC) patients receiving bevacizumab-based first-line treatment. Methods: Genomic DNA from blood samples of patients enrolled in FIRE-3 (a global, randomised, open-label, phase 3 trial, between 2007-6-23 and 2012-9-19, discovery cohort: FOLFIRI/bevacizumab arm, n = 107; control cohort: FOLFIRI/cetuximab arm, n = 129) and MAVERICC (a global, randomised, open-label, phase II study, between 2011-8 and 2015-7, in United States, Canada, Estonia, Ireland, Switzerland, Norway, and Portugal. Validation cohort: FOLFIRI/bevacizumab arm, n = 163) trials, was genotyped using the OncoArray-500 K beadchip panel. The impact on OS and PFS of 17 selected SNPs in 7 genes involved in the lipid metabolism pathway (CD36, FABP4, LPCAT1/2, CPT1A, FASN, ACACA) was analysed using Kaplan-Meier curves, the log-rank test for univariate analyses and likelihood ratio tests of Cox proportional hazards regression parameters for multivariable analyses. ORR and SNP associations were evaluated using Chi-square or Fisher's exact tests. Findings: In the discovery cohort, patients with Interpretation: Our study demonstrates for the first time, to our knowledge, that Funding: This work was supported by the National Cancer Institute [P30CA 014089 to H.-J.L.], Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Victoria and Philip Wilson Research Fund, San Pedro Peninsula Cancer Guild, Ming Hsieh Research Fund, Eddie Mahoney Memorial Research Fund, Shanghai Sailing Program (22YF1407000), China National Postdoctoral Program for Innovative Talents (BX20220084), China Postdoctoral Science Foundation (2022M710768), National Natural Science Foundation of China (82202892).

Indexed as

3' UTR, 3′ untranslated regionsACACA, acetyl-coA carboxylaseADD, antiangiogenic drugAIM, ancestry informative markersBevacizumabBiomarkerCEU, Utah residents with Northern and Western European ancestry from the CEPH collectionColorectal cancerCORECT, Colorectal Cancer TransdisciplinaryCPT1A, carnitine palmitoyl transferase 1ACRC, colorectal cancerECOG PS, Eastern Cooperative Oncology Group performance statusFAO, fatty acids β-oxidationFASN, fatty acid synthaseLipid metabolismLPCAT1, lysolecithin acyltransferase 1LPCAT2, lysolecithin acyltransferase 2MAF, minor allele frequencymCRC, metastatic colorectal cancerMUFA, monounsaturated fatty acidsORR, overall response rateOS, overall survivalPFS, progression-free survivalSNP, single nucleotide polymorphisms

Identifiers

PMID36816347
PMCPMC9932345
OpenAlexW4319227407

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.