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Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives
Open accessAbstract
Epidermal growth factor receptor (EGFR) inhibitors are valuable therapeutics in metastatic colorectal cancer (mCRC). Anti-EGFR monoclonal antibodies (MoAbs), such as cetuximab or panitumumab, in combination with chemotherapy are effective treatment options for patients with RAS and BRAF wild-type mCRC. Nevertheless, several issues are still open concerning the optimal use of anti-EGFR drugs in the continuum of care of mCRC. Novel approaches for increasing the efficacy of anti-EGFR therapies include better molecular selection of EGFR-dependent mCRC, intensification of chemotherapy, combination of anti-EGFR MoAbs and immune checkpoint inhibitors, and reintroduction of EGFR blockade or 'rechallenge' in selected patients who have previously responded to anti-EGFR MoAb therapy. An extensive translational research program was conducted in the Cetuximab After Progression in KRAS wIld-type colorectal cancer patients-Gruppo Oncologico dell' Italia Meridionale (CAPRI-GOIM) study with the aims of determining which subgroups of patients could benefit from the continuous inhibition of EGFR, from evaluating the role of liquid biopsy-based and its concordance with tissue-based molecular testing, and from investigating novel potential mechanisms of resistance to anti-EGFR therapies. In this review, we summarize the translational and clinical findings of the CAPRI-GOIM program in the context of the current knowledge of therapeutic strategies and of ongoing research on more appropriate uses of anti-EGFR therapies in RAS and BRAF wild-type mCRC patients.
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“EGFR is required for CRC progression and treatment response [28–30]”
From Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer (2023) · cites this paper as [30]
Experimental — accuracy not yet measuredIn the citing paper
“Phosphorylation of MET induces the activation of PI3K/AKT and RAS/RAF/MAPK cascades to rescue tumour cells from EGFR inhibitors [120].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [120]
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Metadata
- Authors
- Martinelli, E., Ciardiello, D., Martini, G., Troiani, T., Cardone, C., Vitiello, P. P., Normanno, N., Rachiglio, A. M., Maiello, E., Latiano, T., De Vita, F., & Ciardiello, F.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Casa Sollievo della Sofferenza (IT)
- Corresponding author
- Ciardiello, F.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 31
- Issue
- 1
- Pages
- 30-40
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2999771324
- Cited by
- 225
- References
- 91
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 32 · 2023: 42 · 2022: 66 · 2021: 32 · 2020: 16
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Regione Campania
- Sanofi
- Amgen
- Merck KgA
- Roche
- Servier
- Bayer
- Array
- MSD
- BMS
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- EGFR inhibitors, metastatic colorectal cancer, cetuximab, panitumumab, RAS wild-type, BRAF wild-type, drug rechallenge, immune checkpoint inhibitors, liquid biopsy, resistance mechanisms, molecular selection, chemotherapy intensification
- MeSH terms
- Cetuximab, Panitumumab, Antineoplastic Agents, Humans, Mutation, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), ErbB Receptors
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