When molecular biology transforms clinical oncology: the EGFR journey in colorectal cancer
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...
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| Published in: | Molecular oncology |
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29-10-2024
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Author | Saoudi González, Nadia Bardelli, Alberto Vitiello, Pietro Paolo |
| Author_xml | – sequence: 1 givenname: Pietro Paolo surname: Vitiello fullname: Vitiello, Pietro Paolo organization: IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy – sequence: 2 givenname: Nadia surname: Saoudi González fullname: Saoudi González, Nadia organization: Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain – sequence: 3 givenname: Alberto orcidid: 0000-0003-1647-5070 surname: Bardelli fullname: Bardelli, Alberto organization: IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39470386$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1158/2159-8290.CD-20-0187 10.1158/0008-5472.CAN-06-0191 10.1038/nature11219 10.1196/annals.1315.017 10.1038/nm.3870 10.1016/1040-8428(94)00144-I 10.1038/290516a0 10.1038/nature11156 10.1200/JCO.2006.08.1620 10.1200/JCO.2004.10.182 10.1074/jbc.273.32.19925 10.1038/sj.onc.1204082 10.1038/s41571-021-00495-z 10.1158/0008-5472.CAN-06-4158 10.1038/s41591-022-01886-0 10.1038/nature10868 |
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| Copyright | 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. |
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| Keywords | precision medicine translational research colorectal cancer drug resistance EGFR |
| Language | English |
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| References_xml | – volume: 10 start-page: 1129 issue: 8 year: 2020 ident: e_1_2_6_15_1 article-title: EGFR blockade reverts resistance to KRASG12C inhibition in colorectal cancer publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-20-0187 contributor: fullname: Amodio V – volume: 66 start-page: 3992 issue: 8 year: 2006 ident: e_1_2_6_9_1 article-title: KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-06-0191 contributor: fullname: Lièvre A – volume: 486 start-page: 537 issue: 7404 year: 2012 ident: e_1_2_6_11_1 article-title: The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers publication-title: Nature doi: 10.1038/nature11219 contributor: fullname: Diaz LA – volume: 1038 start-page: 98 issue: 1 year: 2004 ident: e_1_2_6_17_1 article-title: Origins of growth factors: NGF and EGF publication-title: Ann N Y Acad Sci doi: 10.1196/annals.1315.017 contributor: fullname: Cohen S – volume: 21 start-page: 795 issue: 7 year: 2015 ident: e_1_2_6_12_1 article-title: Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients publication-title: Nat Med doi: 10.1038/nm.3870 contributor: fullname: Siravegna G – volume: 19 start-page: 183 issue: 3 year: 1995 ident: e_1_2_6_4_1 article-title: Epidermal growth factor‐related peptides and their receptors in human malignancies publication-title: Crit Rev Oncol Hematol doi: 10.1016/1040-8428(94)00144-I contributor: fullname: Salomon DS – volume: 290 start-page: 516 issue: 5806 year: 1981 ident: e_1_2_6_2_1 article-title: Purified EGF receptor‐kinase interacts specifically with antibodies to Rous sarcoma virus transforming protein publication-title: Nature doi: 10.1038/290516a0 contributor: fullname: Chinkers M – ident: e_1_2_6_10_1 doi: 10.1038/nature11156 – volume: 25 start-page: 1658 issue: 13 year: 2007 ident: e_1_2_6_7_1 article-title: Open‐label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy‐refractory metastatic colorectal cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2006.08.1620 contributor: fullname: Van Cutsem E – volume: 22 start-page: 1201 issue: 7 year: 2004 ident: e_1_2_6_6_1 article-title: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor publication-title: J Clin Oncol doi: 10.1200/JCO.2004.10.182 contributor: fullname: Saltz LB – volume: 273 start-page: 19925 issue: 32 year: 1998 ident: e_1_2_6_3_1 article-title: Increasing complexity of the Ras signaling pathway publication-title: J Biol Chem doi: 10.1074/jbc.273.32.19925 contributor: fullname: Vojtek AB – ident: e_1_2_6_5_1 doi: 10.1038/sj.onc.1204082 – volume: 18 start-page: 506 issue: 8 year: 2021 ident: e_1_2_6_16_1 article-title: Precision oncology in metastatic colorectal cancer – from biology to medicine publication-title: Nat Rev Clin Oncol doi: 10.1038/s41571-021-00495-z contributor: fullname: Di Nicolantonio F – volume: 67 start-page: 2643 issue: 6 year: 2007 ident: e_1_2_6_8_1 article-title: Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti‐epidermal growth factor receptor antibody therapies publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-06-4158 contributor: fullname: Benvenuti S – volume: 28 start-page: 1612 issue: 8 year: 2022 ident: e_1_2_6_13_1 article-title: Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial publication-title: Nat Med doi: 10.1038/s41591-022-01886-0 contributor: fullname: Sartore‐Bianchi A – volume: 483 start-page: 100 issue: 7387 year: 2012 ident: e_1_2_6_14_1 article-title: Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR publication-title: Nature doi: 10.1038/nature10868 contributor: fullname: Prahallad A |
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