Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer
Genomic studies performed through liquid biopsies widely elucidated the evolutionary trajectory of RAS mutant clones under the selective pressure of EGFR inhibitors in patients with wild type RAS primary colorectal tumors. Similarly, the disappearance of RAS mutant clones in plasma has been more rec...
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MDPI AG
2019-01-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/11/1/42 |
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doaj-b46437b452964fba8c6791569c6dfb062020-11-25T00:33:50ZengMDPI AGCancers2072-66942019-01-011114210.3390/cancers11010042cancers11010042Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal CancerCristina Raimondi0Chiara Nicolazzo1Francesca Belardinilli2Flavia Loreni3Angela Gradilone4Yasaman Mahdavian5Alain Gelibter6Giuseppe Giannini7Enrico Cortesi8Paola Gazzaniga9Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, V.le Regina Elena 324, 00161 Rome, ItalyGenomic studies performed through liquid biopsies widely elucidated the evolutionary trajectory of RAS mutant clones under the selective pressure of EGFR inhibitors in patients with wild type RAS primary colorectal tumors. Similarly, the disappearance of RAS mutant clones in plasma has been more recently reported in some patients with primary RAS mutant cancers, supporting for the first time an unexpected negative selection of RAS mutations during the clonal evolution of mCRC. To date, the extent of conversion to RAS wild type disease at the time of progression has not been clarified yet. As a proof of concept, we prospectively enrolled mCRC patients progressing under anti-VEGF based treatments. Idylla™ system was used to screen RAS mutations in plasma and the wild type status of RAS was further confirmed through IT-PGM (Ion Torrent Personal Genome Machine) sequencing. RAS was found mutant in 55% of cases, retaining the same plasma mutation as in the primary tumor at diagnosis, while it was found wild-type in 45%. Four patients testing negative for RAS mutations in plasma at the time of progression of disease (PD) were considered eligible for treatment with EGFR inhibitors and treated accordingly, achieving a clinical benefit. We here propose a hypothetical algorithm that accounts for the transient disappearance of RAS mutant clones over time, which might extend the continuum of care of mutant RAS colorectal cancer patients through the delivery of a further line of therapy.http://www.mdpi.com/2072-6694/11/1/42metastatic colorectal cancercirculating tumor DNARASEGFR inhibitors |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Cristina Raimondi Chiara Nicolazzo Francesca Belardinilli Flavia Loreni Angela Gradilone Yasaman Mahdavian Alain Gelibter Giuseppe Giannini Enrico Cortesi Paola Gazzaniga |
| spellingShingle |
Cristina Raimondi Chiara Nicolazzo Francesca Belardinilli Flavia Loreni Angela Gradilone Yasaman Mahdavian Alain Gelibter Giuseppe Giannini Enrico Cortesi Paola Gazzaniga Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer Cancers metastatic colorectal cancer circulating tumor DNA RAS EGFR inhibitors |
| author_facet |
Cristina Raimondi Chiara Nicolazzo Francesca Belardinilli Flavia Loreni Angela Gradilone Yasaman Mahdavian Alain Gelibter Giuseppe Giannini Enrico Cortesi Paola Gazzaniga |
| author_sort |
Cristina Raimondi |
| title |
Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer |
| title_short |
Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer |
| title_full |
Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer |
| title_fullStr |
Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer |
| title_full_unstemmed |
Transient Disappearance of RAS Mutant Clones in Plasma: A Counterintuitive Clinical Use of EGFR Inhibitors in RAS Mutant Metastatic Colorectal Cancer |
| title_sort |
transient disappearance of ras mutant clones in plasma: a counterintuitive clinical use of egfr inhibitors in ras mutant metastatic colorectal cancer |
| publisher |
MDPI AG |
| series |
Cancers |
| issn |
2072-6694 |
| publishDate |
2019-01-01 |
| description |
Genomic studies performed through liquid biopsies widely elucidated the evolutionary trajectory of RAS mutant clones under the selective pressure of EGFR inhibitors in patients with wild type RAS primary colorectal tumors. Similarly, the disappearance of RAS mutant clones in plasma has been more recently reported in some patients with primary RAS mutant cancers, supporting for the first time an unexpected negative selection of RAS mutations during the clonal evolution of mCRC. To date, the extent of conversion to RAS wild type disease at the time of progression has not been clarified yet. As a proof of concept, we prospectively enrolled mCRC patients progressing under anti-VEGF based treatments. Idylla™ system was used to screen RAS mutations in plasma and the wild type status of RAS was further confirmed through IT-PGM (Ion Torrent Personal Genome Machine) sequencing. RAS was found mutant in 55% of cases, retaining the same plasma mutation as in the primary tumor at diagnosis, while it was found wild-type in 45%. Four patients testing negative for RAS mutations in plasma at the time of progression of disease (PD) were considered eligible for treatment with EGFR inhibitors and treated accordingly, achieving a clinical benefit. We here propose a hypothetical algorithm that accounts for the transient disappearance of RAS mutant clones over time, which might extend the continuum of care of mutant RAS colorectal cancer patients through the delivery of a further line of therapy. |
| topic |
metastatic colorectal cancer circulating tumor DNA RAS EGFR inhibitors |
| url |
http://www.mdpi.com/2072-6694/11/1/42 |
| work_keys_str_mv |
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