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Cancers
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Cetuximab and Cancer
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Cetuximab and Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (1 August 2023) | Viewed by 6870

Special Issue Editors

Prof. Dr. Fortunato Ciardiello

E-Mail Website
Guest Editor
Oncology Unit, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy
Interests: colorectal cancer; NSCLC; anti-EGFR; anti-HER2; BRAF inhibitors; immunotherapy; liquid biopsy; precision medicine
Dr. Davide Ciardiello

E-Mail Website
Guest Editor
Oncology Unit, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy
Interests: colorectal cancer; gastrointestinal malignancies; immunotherapy; liquid biopsy; precision medicine; rechallenge
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

During the last 30 years, a better understanding of the multifaced role of the epidermal growth factor signaling pathway in the pathogenesis of epithelial malignancies has led to the clinical development of different selective inhibitors.

Cetuximab is a first-class humanized IgG 1 monoclonal antibody highly selective for the extracellular domain of the epidermal growth factor receptor (EGFR). Intriguingly, cetuximab could exert antitumor activity not only by blocking the EGFR signaling cascade, but also by inducing antibody-dependent cell-mediated cytotoxicity (ADCC).

The use of cetuximab in combination with chemotherapy represents a standard of care as first-line treatment for RAS wild-type metastatic colorectal cancer (CRC) and recurrent/metastatic head and neck cancer. More recently, the combination of cetuximab and the BRAF inhibitor encorafenib has been considered the best treatment option for pretreated BRAFV600E mutant colorectal cancer. Furthermore, new evidence suggests that rechallenge with cetuximab in combination with chemotherapy/immunotherapy could exert antitumor activity in pre-treated RAS wild-type colorectal cancer.

To date, there are different matters of debate, including the optimization of available treatments, development of new combinatory strategies, identification of novel predictive biomarkers of response, and management of toxicities.

In this Special Issue, original research articles and reviews regarding the role of cetuximab in cancer are welcome.

We look forward to receiving your contributions.

Prof. Dr. Fortunato Ciardiello
Dr. Davide Ciardiello
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cetuximab
  • anti-EGFR
  • colorectal cancer
  • head and neck cancer
  • skin toxicities
  • biomarkers
  • rechallenge
  • combinatory strategies

Published Papers (4 papers)

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Research

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12 pages, 4682 KiB  
Article
Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer—A Multicentre Propensity-Score-Matched Retrospective Analysis
by Vincenzo Formica, Cristina Morelli, Veronica Conca, Maria Alessandra Calegari, Jessica Lucchetti, Emanuela Dell’Aquila, Marta Schirripa, Marco Messina, Lisa Salvatore, Federica Lo Prinzi, Giovanni Dima, Giovanni Trovato, Silvia Riondino, Mario Roselli, Ferdinandos Skoulidis, Hendrik-Tobias Arkenau and Chiara Cremolini
Cancers 2023, 15(11), 3064; https://doi.org/10.3390/cancers15113064 - 05 Jun 2023
Viewed by 1848
Abstract
Background: KRASG12C-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRASG12C-inhibitor might [...] Read more.
Background: KRASG12C-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. Methods: A multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/− bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment–effect interactions. KRASG12D-mutated patients were analysed as control. Results: One hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. However, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. No difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). Conclusions: First-line irinotecan-based regimens provided better survival results in KRASG12C-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations. Full article
(This article belongs to the Special Issue Cetuximab and Cancer)
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11 pages, 1117 KiB  
Article
Pretreatment Plasma Circulating Tumor DNA RAS/BRAF Mutational Status in Refractory Metastatic Colorectal Cancer Patients Who Are Candidates for Anti-EGFR Rechallenge Therapy: A Pooled Analysis of the CAVE and VELO Clinical Trials
by Davide Ciardiello, Stefania Napolitano, Vincenzo Famiglietti, Lucia Esposito, Vincenzo De Falco, Alessandra Di Liello, Antonio Avallone, Evaristo Maiello, Filippo Pietrantonio, Chiara Cremolini, Maria Giulia Zampino, Nicola Fazio, Teresa Troiani, Erika Martinelli, Fortunato Ciardiello and Giulia Martini
Cancers 2023, 15(7), 2117; https://doi.org/10.3390/cancers15072117 - 01 Apr 2023
Cited by 5 | Viewed by 1675
Abstract
Rechallenge with anti-EGFR drugs represents a promising strategy in refractory RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC). We performed the pooled analysis of the CAVE and VELO studies to evaluate the percentage of patients with WT circulating tumor DNA (ctDNA) tumors [...] Read more.
Rechallenge with anti-EGFR drugs represents a promising strategy in refractory RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC). We performed the pooled analysis of the CAVE and VELO studies to evaluate the percentage of patients with WT circulating tumor DNA (ctDNA) tumors and the association of mutational status with time from the last anti-EGFR drug administration. At baseline, 97/129 patients had RAS/BRAF WT plasma ctDNA, while 32/129 had RAS/BRAF mutated plasma ctDNA. Median anti-EGFR drug-free interval was 10.6 (CI 95%, 8.9–13.4) months in the plasma RAS/BRAF mutant group as compared to 13.0 (CI 95%, 11.1–16.6) months in RAS/BRAF WT group (p = 0.169). To investigate the time window of the RAS/BRAF mutant cancer cell clone disappearance, descriptive analysis using different time points was performed. No difference in the proportion of patients whose baseline plasma ctDNA was RAS/BRAF WT or mutated was found between 4 and 18 months since the last administration of anti-EGFR drugs. In contrast, 38/44 of patients with anti-EGFR drug-free interval of 18 months or more displayed a ctDNA RAS/BRAF WT status. Taken together, these results shows that the length of anti-EGFR free interval is not a sufficient criterion for patient selection, supporting the role of liquid biopsies for improving treatment efficacy. Full article
(This article belongs to the Special Issue Cetuximab and Cancer)
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Review

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18 pages, 756 KiB  
Review
Cetuximab as a Key Partner in Personalized Targeted Therapy for Metastatic Colorectal Cancer
by Nadia Saoudi González, Javier Ros, Iosune Baraibar, Francesc Salvà, Marta Rodríguez-Castells, Adriana Alcaraz, Ariadna García, Josep Tabernero and Elena Élez
Cancers 2024, 16(2), 412; https://doi.org/10.3390/cancers16020412 - 18 Jan 2024
Viewed by 1402
Abstract
Cetuximab, a chimeric IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has revolutionized personalized treatment of metastatic colorectal cancer (mCRC) patients. This review highlights the mechanism of action, characteristics, and optimal indications for cetuximab in mCRC. Cetuximab has emerged as a [...] Read more.
Cetuximab, a chimeric IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has revolutionized personalized treatment of metastatic colorectal cancer (mCRC) patients. This review highlights the mechanism of action, characteristics, and optimal indications for cetuximab in mCRC. Cetuximab has emerged as a pivotal partner for novel therapies in specific molecular subgroups, including BRAF V600E, KRAS G12C, and HER2-altered mCRC. Combining cetuximab with immunotherapy and other targeted agents further expands the therapeutic landscape, offering renewed hope for mCRC patients who face the development of resistance to conventional therapies. Ongoing clinical trials have continued to uncover innovative cetuximab-based treatment strategies, promising a brighter future for mCRC patients. This review provides a comprehensive overview of cetuximab’s role and its evolving importance in personalized targeted therapy of mCRC patients, offering valuable insights into the evolving landscape of colorectal cancer treatment. Full article
(This article belongs to the Special Issue Cetuximab and Cancer)
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Other

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10 pages, 673 KiB  
Commentary
Co-Targeting the EGFR and PI3K/Akt Pathway to Overcome Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma: What about Autophagy?
by Hannah Zaryouh, Jinthe Van Loenhout, Marc Peeters, Jan Baptist Vermorken, Filip Lardon and An Wouters
Cancers 2022, 14(24), 6128; https://doi.org/10.3390/cancers14246128 - 12 Dec 2022
Cited by 2 | Viewed by 1312
Abstract
Resistance to EGFR-targeted therapy is a major obstacle on the road to effective treatment options for head and neck cancers. During the search for underlying mechanisms and regulators of this resistance, there were several indications that EGFR-targeted therapy resistance is (partially) mediated by [...] Read more.
Resistance to EGFR-targeted therapy is a major obstacle on the road to effective treatment options for head and neck cancers. During the search for underlying mechanisms and regulators of this resistance, there were several indications that EGFR-targeted therapy resistance is (partially) mediated by aberrant signaling of the PI3K/Akt pathway. Genomic alterations in and/or overexpression of major components of the PI3K/Akt pathway are common in HNSCC tumors. Therefore, downstream effectors of the PI3K/Akt pathway serve as promising targets in the search for novel therapeutic strategies overcoming resistance to EGFR inhibitors. As both the EGFR/Ras/Raf/MAPK and the PI3K/Akt pathway are involved in autophagy, combinations of EGFR and PI3K/Akt pathway inhibitors can induce an autophagic response in tumor cells. This activation of autophagy can be seen as a “double-edge sword”, depending on the cellular context. Autophagy is largely known as a cytoprotective mechanism, but it can also be a mechanism of programmed (autophagic) cell death. The activation of autophagy during anti-cancer treatment is, therefore, not necessarily a bad sign. However, in HNSCC, the role of therapy-induced autophagy as an anti-tumor mechanism is still largely unclear. Further research is warranted to understand the potential of combination treatments targeting both the EGFR and PI3K/Akt pathway. Full article
(This article belongs to the Special Issue Cetuximab and Cancer)
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