Cargando…

Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer

BACKGROUND: Treatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail t...

Descripción completa

Detalles Bibliográficos
Autores principales: Sagawa, Tamotsu, Sato, Yasushi, Hirakawa, Masahiro, Hamaguchi, Kyoko, Tamura, Fumito, Nagashima, Hiroyuki, Fujikawa, Koshi, Okamoto, Koichi, Kawano, Yutaka, Sogabe, Masahiro, Miyamoto, Hiroshi, Takayama, Tetsuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332633/
https://www.ncbi.nlm.nih.gov/pubmed/37434969
http://dx.doi.org/10.3389/fonc.2023.1203296
_version_ 1785070477331398656
author Sagawa, Tamotsu
Sato, Yasushi
Hirakawa, Masahiro
Hamaguchi, Kyoko
Tamura, Fumito
Nagashima, Hiroyuki
Fujikawa, Koshi
Okamoto, Koichi
Kawano, Yutaka
Sogabe, Masahiro
Miyamoto, Hiroshi
Takayama, Tetsuji
author_facet Sagawa, Tamotsu
Sato, Yasushi
Hirakawa, Masahiro
Hamaguchi, Kyoko
Tamura, Fumito
Nagashima, Hiroyuki
Fujikawa, Koshi
Okamoto, Koichi
Kawano, Yutaka
Sogabe, Masahiro
Miyamoto, Hiroshi
Takayama, Tetsuji
author_sort Sagawa, Tamotsu
collection PubMed
description BACKGROUND: Treatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail to respond. Secondary mutations in the mitogen-activated protein (MAPK) signaling pathway (mainly in NRAS and BRAF) have been implicated in anti-EGFR resistance. However, the process by which resistant clones develop during therapy has not been elucidated, and considerable intrapatient and interpatient heterogeneity exists. Circulating tumor DNA (ctDNA) testing has recently allowed the noninvasive detection of heterogeneous molecular alterations that underlie the evolution of resistance to anti-EGFR. In this report, we describe our observation of genomic alterations in KRAS and NRAS in a patient with acquired resistance to anti-EGFR antibody drugs by tracking clonal evolution using serial ctDNA anaylsis. CASE PRESENTATION: A 54-year-old woman was initially diagnosed with sigmoid colon cancer with multiple liver metastases. After receiving first-line mFOLFOX + cetuximab, second-line FOLFIRI + ramucirumab, third-line trifluridine/tipiracil + bevacizumab, fourth-line regorafenib, and fifth-line CAPOX + bevacizumab, she was rechallenged with CPT-11 + cetuximab. The best response to anti-EGFR rechallenge therapy was a partial response. RAS in the ctDNA was assessed during treatment. The RAS status changed from wild type to mutant type, back to wild type, and again to mutant type (NRAS/KRAS codon 61) during the course of treatment. CONCLUSION: In this report, tracking of ctDNA allowed us to describe clonal evolution in a case in which we observed genomic alterations in KRAS and NRAS in a patient who acquired resistance to anti-EGFR antibody drugs during treatment. It is reasonable to consider repeat molecular interrogation during progression in patients with mCRC by using ctDNA analysis, which could help to identify patients who may benefit from a rechallenge strategy.
format Online
Article
Text
id pubmed-10332633
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-103326332023-07-11 Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer Sagawa, Tamotsu Sato, Yasushi Hirakawa, Masahiro Hamaguchi, Kyoko Tamura, Fumito Nagashima, Hiroyuki Fujikawa, Koshi Okamoto, Koichi Kawano, Yutaka Sogabe, Masahiro Miyamoto, Hiroshi Takayama, Tetsuji Front Oncol Oncology BACKGROUND: Treatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail to respond. Secondary mutations in the mitogen-activated protein (MAPK) signaling pathway (mainly in NRAS and BRAF) have been implicated in anti-EGFR resistance. However, the process by which resistant clones develop during therapy has not been elucidated, and considerable intrapatient and interpatient heterogeneity exists. Circulating tumor DNA (ctDNA) testing has recently allowed the noninvasive detection of heterogeneous molecular alterations that underlie the evolution of resistance to anti-EGFR. In this report, we describe our observation of genomic alterations in KRAS and NRAS in a patient with acquired resistance to anti-EGFR antibody drugs by tracking clonal evolution using serial ctDNA anaylsis. CASE PRESENTATION: A 54-year-old woman was initially diagnosed with sigmoid colon cancer with multiple liver metastases. After receiving first-line mFOLFOX + cetuximab, second-line FOLFIRI + ramucirumab, third-line trifluridine/tipiracil + bevacizumab, fourth-line regorafenib, and fifth-line CAPOX + bevacizumab, she was rechallenged with CPT-11 + cetuximab. The best response to anti-EGFR rechallenge therapy was a partial response. RAS in the ctDNA was assessed during treatment. The RAS status changed from wild type to mutant type, back to wild type, and again to mutant type (NRAS/KRAS codon 61) during the course of treatment. CONCLUSION: In this report, tracking of ctDNA allowed us to describe clonal evolution in a case in which we observed genomic alterations in KRAS and NRAS in a patient who acquired resistance to anti-EGFR antibody drugs during treatment. It is reasonable to consider repeat molecular interrogation during progression in patients with mCRC by using ctDNA analysis, which could help to identify patients who may benefit from a rechallenge strategy. Frontiers Media S.A. 2023-06-26 /pmc/articles/PMC10332633/ /pubmed/37434969 http://dx.doi.org/10.3389/fonc.2023.1203296 Text en Copyright © 2023 Sagawa, Sato, Hirakawa, Hamaguchi, Tamura, Nagashima, Fujikawa, Okamoto, Kawano, Sogabe, Miyamoto and Takayama https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Sagawa, Tamotsu
Sato, Yasushi
Hirakawa, Masahiro
Hamaguchi, Kyoko
Tamura, Fumito
Nagashima, Hiroyuki
Fujikawa, Koshi
Okamoto, Koichi
Kawano, Yutaka
Sogabe, Masahiro
Miyamoto, Hiroshi
Takayama, Tetsuji
Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
title Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
title_full Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
title_fullStr Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
title_full_unstemmed Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
title_short Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
title_sort case report: longitudinal monitoring of clonal evolution by circulating tumor dna for resistance to anti-egfr antibody in a case of metastatic colorectal cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332633/
https://www.ncbi.nlm.nih.gov/pubmed/37434969
http://dx.doi.org/10.3389/fonc.2023.1203296
work_keys_str_mv AT sagawatamotsu casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT satoyasushi casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT hirakawamasahiro casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT hamaguchikyoko casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT tamurafumito casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT nagashimahiroyuki casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT fujikawakoshi casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT okamotokoichi casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT kawanoyutaka casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT sogabemasahiro casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT miyamotohiroshi casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer
AT takayamatetsuji casereportlongitudinalmonitoringofclonalevolutionbycirculatingtumordnaforresistancetoantiegfrantibodyinacaseofmetastaticcolorectalcancer