scholarly journals Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 6813
Author(s):  
Chiara Guarini ◽  
Teresa Grassi ◽  
Gaetano Pezzicoli ◽  
Camillo Porta
Keyword(s):  
Colorectal Cancer ◽  
Somatic Mutations ◽  
Clinical Evidence ◽  
Advanced Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarker ◽  
Therapeutic Implications ◽  
Oncogenic Driver ◽  
Epidermal Growth

The human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver and a successful therapeutic target in several malignancies, such as breast and gastric cancers. HER2 alterations, including amplification and somatic mutations, have also been detected in a small but not negligible subset of patients affected by advanced colorectal cancer (aCRC). However, to date, there are no available oncotargets in this malignancy beyond RAS and BRAF that are available. Here we present an overview on the present predictive and prognostic role of HER2 expression in aCRC, as well as on its consequent potential therapeutic implications from preclinical investigations towards ongoing trials testing anti-HER2 agents in aCRC. While HER2′s role as a molecular predictive biomarker for anti-EGFR therapies in CRC is recognized, HER2 prognostic value remains controversial. Moreover, thanks to the impressive and growing body of clinical evidence, HER2 is strongly emerging as a new potential actionable oncotarget in aCRC. In conclusion, in the foreseeable future, HER2-targeted therapeutic strategies may integrate the algorithm of aCRC treatment towards an increasingly tailored therapeutic approach to this disease.

Epidermal growth factor receptor (EGFR) serum level may predict response in patients with advanced colorectal cancer (ACC) treated with gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4119-4119 ◽  
Author(s):  
M. G. Zampino ◽  
E. Magni ◽  
L. Zorzino ◽  
L. Santoro ◽  
C. Massacesi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Progressive Disease ◽  
Advanced Colorectal Cancer ◽  
Objective Response ◽  
Surrogate Marker ◽  
Growth Factor Receptor ◽  
Binding Domain ◽  
Serum Samples ◽  
Cox's Regression ◽  
Epidermal Growth

4119 Background: EGFR-overexpression reported in colorectal cancer, justifies use of EGFR inhibitors. We conducted a phase II study (ESMO 2005) in ACC with the aim to assess efficacy of gefitinib plus oxaliplatin containing regimen. Main biological objective was to assess serum EGFR extra-cellular binding domain as surrogate marker of tyrosine-kinase inhibition and as predictor of outcome. Methods: 57 patients with EGFR-positive ACC,received gefitinib 250 mg/day combined with simplified FOLFOX-6 for at least 4 cycles,for a maximum of 10 courses.In not progressive disease, gefitinib was continued as maintenance treatment. Tumour assessment by RECIST criteria was performed at baseline and every 4 cycles.Serum EGFR extracellular binding-domain was evaluated by quantitative enzyme-linked immunoadsorbent.Serum EGFR as predictive factor was evaluated both taking into account the basal value only,and the whole EGFR pattern over time.The analyses were performed by logistic and Cox’s regression model with time-dependent covariate respectively;both models included centre, gender,age and site of primary tumours as adjusting factors. Results: Serum samples for EGFR were obtained at baseline and at every assessment.During mono-therapy phase the patients with serum samples decreased. Over treatment,34 patients reported a CR or PR as best objective response (BOR),while 9 patients showed SD or PD. Higher serum EGFR was associated to BOR both at baseline and over time.This result was confirmed by a similar analysis,which considered the whole EGFR profile,instead of the basal value only. Conclusions: Serum EGFR at baseline can be considered a significant predictor for the BOR.This observation is in line with data reported on lung cancer (Gregorc V, 2004).Although the EGFR trend over time seems to confirm the basal difference,this result should be taken with caution,due to the little number of cases reporting EGFR values besides the basal one. [Table: see text] No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document