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.
“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]
The Introduction (page unavailable) calls EGFR a therapeutic target in metastatic CRC, but says anti-EGFR treatment works only in a subset of patients and that identifying tumors truly dependent on EGFR activation remains an open question. The section on novel approaches (page unavailable) describes EGFR expression as contributing to progression in a preclinical model. Neither passage establishes that EGFR is required for CRC progression or treatment response generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPhosphorylation of MET induces the activation of PI3K/AKT and RAS/RAF/MAPK cascades to rescue tumour cells from EGFR inhibitors.
“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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- 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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