Vitiello Pietro Paolo, Saoudi González Nadia, Bardelli Alberto
Department of Oncology, University of Torino, Italy.
IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy.
Mol Oncol. 2025 Feb;19(2):267-270. doi: 10.1002/1878-0261.13754. Epub 2024 Oct 29.
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.
生长因子的发现及其与癌症的关联构成了精准肿瘤学的基础。针对结直肠癌（CRC）中表皮生长因子受体（EGFR）的药物的临床前和临床开发曾伴随着大肆宣传和厚望，尽管此类药物的临床试验遭遇了内在和获得性耐药问题，极大地限制了它们的治疗价值。然而，对CRC中EGFR信号通路生物学的更深入理解，以及用于实时研究癌症演变的液体活检方法的发展，推动了CRC中抗EGFR治疗的临床优化。这种基于生物学知识与临床开发共同演变的工作流程，使得在发现相关治疗耐药机制的同时能够开发绕过这种耐药性的策略。这种范式的更广泛应用可能会取得成功，并为靶向治疗以外的治疗策略在实验室研究与临床应用之间创造一条有效的捷径。
