When molecular biology transforms clinical oncology: the EGFR journey in colorectal cancer

Abstract

Colorectal cancer; Drug resistance; Precision medicine

Cáncer colorrectal; Resistencia a medicamentos; Medicina de precisión

Càncer colorectal; Resistència a medicaments; Medicina de precisió

The discovery of growth factors and their involvement in cancer represents the foundation of precision oncology. The preclinical and clinical development of agents targeting epidermal growth factor receptor (EGFR) in colorectal cancer (CRC) were accompanied by big hype and hopes, though the clinical testing of such agents clashed with intrinsic and acquired resistance, greatly limiting their therapeutic value. However, a better understanding of the biology of the EGFR signaling pathway in CRC, coupled with the development of liquid biopsy methodologies to study cancer evolution in real time, fostered the clinical refinement of anti-EGFR treatment in CRC. Such a workflow, based on the co-evolution of biology knowledge and clinical development, allowed to couple the discovery of relevant therapy resistance mechanisms to the development of strategies to bypass this resistance. A broader application of this paradigm could prove successful and create an effective shortcut between the bench and the bedside for treatment strategies other than targeted therapy.

AB is supported by: FONDAZIONE AIRC under 5 per Mille 2018 – ID. 21091 program – P.I. Alberto Bardelli; AIRC under IG 2023 – ID. 28922 project – P.I. Alberto Bardelli; International Accelerator Award, ACRCelerate, jointly funded by Cancer Research UK (A26825 and A28223), FC AECC (GEACC18004TAB) and AIRC (22795); IMI contract no. 101007937 PERSIST-SEQ; European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (TARGET, grant agreement no. 101020342) – P.I. Alberto Bardelli; PRIN (Progetti di Rilevante Interesse Nazionale) no. 2022CHB9BA – P.I. Alberto Bardelli. NSG is supported by a European Society for Medical Oncology (ESMO) Translational Research Fellowship. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO. Images were generated with biorender.com.