Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial.

Cancer Discovery
Khurum H KhanNicola Valeri

Abstract

Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. RAS pathway aberrations can be tracked in cfDNA to monitor resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer. In this prospective phase II clinical trial of single-agent cetuximab in RAS wild-type patients, we combine genomic profiling of serial cfDNA and matched sequential tissue biopsies with imaging and mathematical modeling of cancer evolution. We show that a significant proportion of patients defined as RAS wild-type based on diagnostic tissue analysis harbor aberrations in the RAS pathway in pretreatment cfDNA and, in fact, do not benefit from EGFR inhibition. We demonstrate that primary and acquired resistance to cetuximab are often of polyclonal nature, and these dynamics can be observed in tissue and plasma. Furthermore, evolutionary modeling combined with frequent serial sampling of cfDNA allows prediction of the expected time to treatment failure in individual patients. This study demonstrates how integrating frequently sampled longitudinal liquid biopsies ...Continue Reading

References

Sep 1, 1988·The New England Journal of Medicine·B VogelsteinJ L Bos
Feb 15, 2008·Nature Reviews. Cancer·Alexander R A Anderson, Vito Quaranta
Mar 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rafael G AmadoDavid D Chang
Feb 5, 2010·Cancer Cell·Alexa B TurkePasi A Jänne
Sep 9, 2011·Science Translational Medicine·Kimio YonesakaPasi A Jänne
Jan 20, 2012·Nature·Mel Greaves, Carlo C Maley
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
May 23, 2012·Cell·Serena Nik-ZainalUNKNOWN Breast Cancer Working Group of the International Cancer Genome Consortium
Dec 12, 2012·Digestive Diseases·David Lieberman
Jun 4, 2014·CA: a Cancer Journal for Clinicians·Carol E DeSantisAhmedin Jemal
Jun 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sebastijan HoborAlberto Bardelli
Oct 9, 2014·Systematic Biology·Niko BeerenwinkelFlorian Markowetz
Jul 8, 2015·Nature Medicine·Giulia SiravegnaAlberto Bardelli
Jul 15, 2015·Nature Reviews. Cancer·Doris P Tabassum, Kornelia Polyak
Aug 28, 2015·Science Translational Medicine·Isaac Garcia-MurillasNicholas C Turner
Sep 24, 2015·Nature Communications·Sandra MisaleAlberto Bardelli
Sep 30, 2015·Nature·Andrea BertottiVictor E Velculescu
Dec 9, 2015·Cancer Discovery·Mariangela RussoRyan B Corcoran
Jan 27, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Andrew RowlandMichael J Sorich
Apr 6, 2016·Nature Communications·John M FindlayIan Tomlinson
Dec 9, 2016·Nature Communications·Beth O Van EmburghAlberto Bardelli
Feb 12, 2017·Cell·Nicholas McGranahan, Charles Swanton
Feb 16, 2017·Cancer Cell·Alberto Bardelli, Klaus Pantel
Mar 23, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D SantiniG Tonini
Mar 23, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H LoteN Valeri
Apr 4, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J GrasselliA Vivancos
Apr 13, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alain R ThierryScott Kopetz
Apr 27, 2017·Nature·Christopher AbboshCharles Swanton
May 4, 2017·Genome Research·Ayesha NooraniUNKNOWN Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Jul 8, 2017·Science·Kamila NaxerovaRakesh K Jain
Sep 28, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N NormannoUNKNOWN CAPRI-GOIM Investigators

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Citations

Jan 17, 2019·Expert Review of Molecular Diagnostics·Claire FranczakAlexandre Harlé
Mar 5, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Chiara BraconiJesper B Andersen
Mar 29, 2019·Nature Reviews. Genetics·Samra TurajlicCharles Swanton
Jul 4, 2019·JAMA Oncology·Gayathri Anandappa, David Cunningham
Apr 22, 2020·Proceedings. Biological Sciences·Mark GluzmanAlexander Vladimirsky
Nov 15, 2018·ESMO Open·Desamparados RodaAndrés Cervantes
May 31, 2020·Cancers·Drahomír KolenčíkPeter Kuhn
Aug 29, 2019·Nature Reviews. Cancer·Johannes G ReiterBert Vogelstein
Dec 13, 2019·Pharmacogenomics·Jaana Oikkonen, Sampsa Hautaniemi
Mar 30, 2020·Nature Communications·George D CresswellAndrea Sottoriva
Aug 13, 2020·Therapeutic Advances in Medical Oncology·Giulia MartiniElena Elez
May 7, 2019·Annual Review of Genomics and Human Genetics·Marc J WilliamsTrevor A Graham
Nov 2, 2019·Cancer Cell International·Maria PalmieriElisa Frullanti
Apr 4, 2020·Pharmacogenomics·Ioannis D KyrochristosDimitrios H Roukos
Sep 25, 2020·British Journal of Cancer·Laura KellerKlaus Pantel
May 3, 2019·JCO Precision Oncology·Jaana OikkonenSampsa Hautaniemi
Oct 4, 2018·Nature Reviews. Gastroenterology & Hepatology·Clemens Thoma
Nov 7, 2018·Cold Spring Harbor Perspectives in Medicine·Elaine R Mardis
Mar 31, 2019·Genome Medicine·Matthew W Fittall, Peter Van Loo
Apr 4, 2019·Molecular Diagnosis & Therapy·Re-I ChinAadel A Chaudhuri
Mar 21, 2020·European Radiology·Marco CalandriBruno C Odisio
Sep 5, 2020·Cancer Management and Research·Qimin TuJianfei Luo
May 28, 2019·Current Colorectal Cancer Reports·Rebecca A DeStefanisDustin A Deming
Feb 27, 2020·Nature Communications·Benjamin WernerAndrea Sottoriva
Aug 30, 2020·Biomedicines·Marco VacanteAntonio Biondi
Dec 4, 2019·Nature Reviews. Gastroenterology & Hepatology·Amanda J CraigAugusto Villanueva
Oct 29, 2020·JCO Clinical Cancer Informatics·James W T Yates, Hitesh Mistry
Nov 10, 2020·CA: a Cancer Journal for Clinicians·Michael L ChengGeoffrey R Oxnard
Oct 4, 2018·Cancer Discovery·Giulia Siravegna, Ryan B Corcoran
Jul 3, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christine M ParseghianScott Kopetz
Feb 27, 2020·Molecular Cancer Research : MCR·Alexandros GeorgiouSteven R Whittaker
Feb 28, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giulia SiravegnaAlberto Bardelli

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