ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Gene expression markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Pooled it
- Prognostic value of amphiregulin and epiregulin mRNA expression in metastatic colorectal cancer patients.Oncotarget · 2016Pooled it
- Final Results of ERBIMOX: A Randomized Phase II Study of Modified FOLFOX7 With or Without Cetuximab as First-Line Treatment for KRAS Wild-type Metastatic Colorectal Cancer.Journal of gastrointestinal cancer · 2025Trial
- Association of Tumor HER3 Messenger RNA Expression With Panitumumab Efficacy in Advanced Colorectal Cancer.JAMA oncology · 2018Trial
- Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G.Cancer science · 2016Trial
- Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to anti-EGFR therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Transcriptomic Analysis of Muscle Satellite Cell Regulation on Intramuscular Preadipocyte Differentiation in Tan Sheep.International journal of molecular sciences · 2025Article
- Article
- The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.Acta pharmaceutica Sinica. B · 2024Review
- Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion.International journal of biological sciences · 2024Article
- A Vaccine against Cancer: Can There Be a Possible Strategy to Face the Challenge? Possible Targets and Paradoxical Effects.Vaccines · 2023Review
- Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
- Review
- [Blocking Adenosine/A2AR Pathway for Cancer Therapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain.Pharmacological reviews · 2022Review
- Sustained compensatory p38 MAPK signaling following treatment with MAPK inhibitors induces the immunosuppressive protein CD73 in cancer: combined targeting could improve outcomes.Molecular oncology · 2021Article
- Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Impact of EGFR and EGFR ligand expression on treatment response in patients with metastatic colorectal cancer.Oncology letters · 2021Article
- Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeFormalin-fixed, paraffin-embedded tumor samples from CALGB 80203 were analyzed for expression of EGFR axis-related genes to identify prognostic or predictive biomarkers for cetuximab treatment. PATIENTS AND
methodsPatients (238 total) with first-line metastatic colorectal cancer (mCRC) were randomized to FOLFOX or FOLFIRI chemotherapy ± cetuximab. qRT-PCR analyses were conducted on tissues from 103 patients at baseline to measure gene expression levels of HER-related genes, including amphiregulin (AREG), betacellulin (BTC), NT5E (CD73), DUSP4, EGF, EGFR, epigen (EPGN), epiregulin (EREG), HBEGF, ERBB2 (HER2), ERBB3 (HER3), ERBB4 (HER4), PHLDA1, and TGFA. The interactions between expression levels and treatment with respect to progression-free survival (PFS) and overall survival (OS) were modeled using multiplicative Cox proportional hazards models.
resultsHigh tumor mRNA levels of HER2 [hazard ratio (HR), 0.64; P = 0.002] and EREG (HR, 0.89; P = 0.016) were prognostic markers associated with longer PFS across all patients. HER3 and CD73 expression levels were identified as potential predictive markers of benefit from cetuximab. In KRAS wild-type (WT) tumors, low HER3 expression was associated with longer OS from cetuximab treatment, whereas high HER3 expression was associated with shorter OS from cetuximab treatment (chemo + cetuximab: HR, 1.15; chemo-only: HR, 0.48; Pinteraction = 0.029). High CD73 expression was associated with longer PFS from cetuximab treatment in patients with KRAS-WT (chemo + cetuximab: HR, 0.91; chemo-only: HR, 1.57; Pinteraction = 0.026) and KRAS-mutant (Mut) tumors (chemo + cetuximab: HR, 0.80; chemo-only: HR, 1.29; P = 0.025).
conclusionsGene expression of HER3 and CD73 was identified as a potential predictive marker for cetuximab. These data implicate HER axis signaling and immune modulation as potential mechanisms of cetuximab action and sensitivity.
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