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The EGFR signaling pathway plays a pivotal role in CRC progression and treatment. Therefore, targeted therapies (mAbs) against this marker have been developed and have entered clinical practice. A myriad of studies focused attention on the possibility of predicting the efficacy of EGFR-targeted therapies, and currently the assessment of KRAS and NRAS gene mutations is mandatory before any administration of anti-EGFR mAbs. However, it has also been demonstrated that the molecular characterization of the EGFR pathway, due to technical problems as well as by the co-occurrence of different genetic alterations in the same patient (rendering it difficult to understand the clinical role of the individual alteration), needs to be refined. Therefore, the efforts of molecular pathologists are currently addressed toward investigating the aforementioned problem.

On the other hand, pharmaceutical companies have studied new modalities of the administration of cetuximab and panitumumab, as well as developing new (and hypothetically more efficient) compounds, not only targeted against EGFR, but also against EGFR-downstream members (to be administered in combination with anti-EGFR mAbs). These new options are the object of intensive studies, and may also lead to a substantial improvement for patients affected by an EGFR-addicted CRC.

Given all these considerations, there is reasonable hope that mCRC patients will be better treated in the near future.


The authors report no conflicts of interest in this work.

Piercarlo Saletti,1 Francesca Molinari,2 Sara De Dosso,1 Milo Frattini2

1Oncology Institute of Southern Switzerland, Bellinzona,2Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland


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