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EnglishCetuximab and panitumumab are anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies used as therapies for metastatic colorectal cancer patients. Intrinsic mechanisms of resistance, such as RAS mutations, can prevent patients from having a response with clinical benefit. The clinical efficacy of EGFR targeted antibodies is limited by the development of acquired (secondary) resistance, which typically occurs within 3-12 months from the start of therapy. Preclinical models and analyses of clinical samples have uncovered some of the alterations that confer a selective advantage to tumor cells when under the pressure of anti-EGFR therapy. Molecular profiling of clinical specimens confirmed that genetic alterations of genes in the EGFR-RAS-RAF-MEK signaling pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to anti-EGFR antibodies. The escape from anti-EGFR blockade appears to converge on the (re)activation of MEK-ERK or AKT as revealed in preclinical studies. Circulating tumor DNA and patient derived xenografts have proven useful tools to monitor patients for resistance to anti-EGFR therapy and test combination therapies to overcome or reverse resistance.
Acquired resistance to EGFR-targeted therapies incolorectal cancer / B.O. Van Emburgh, A. Sartore-Bianchi, F. Di Nicolantonio, S. Siena, A. Bardelli. - In: MOLECULAR ONCOLOGY. - ISSN 1574-7891. - 8:6(2014 Sep), pp. 1084-1094.
| Titolo: | Acquired resistance to EGFR-targeted therapies incolorectal cancer |
| Autori: | SIENA, SALVATORE (Penultimo) |
| Parole Chiave: | Acquired resistance; Anti-EGFR therapy; Cetuximab; Colorectal cancer; MET; Panitumumab; RAS; Animals; Antineoplastic Agents; Colon; Colorectal Neoplasms; Humans; MAP Kinase Signaling System; Molecular Targeted Therapy; Proto-Oncogene Proteins c-akt; Receptor, Epidermal Growth Factor; Rectum; Signal Transduction; ras Proteins; Drug Resistance, Neoplasm; Cancer Research; Genetics; Molecular Medicine; Medicine (all) |
| Settore Scientifico Disciplinare: | Settore MED/06 - Oncologia Medica |
| Data di pubblicazione: | set-2014 |
| Rivista: | |
| Tipologia: | Article (author) |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.molonc.2014.05.003 |
| Appare nelle tipologie: | 01 - Articolo su periodico |
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| 2014 Van Emburgh et al Molecular Oncology.pdf | Publisher's version/PDF | Administrator Richiedi una copia |
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