KRAS mutation in colon cancer: a marker of resistance to EGFR-I therapy.

Annals of Surgical Oncology
Ahmad D Siddiqui, Bilal Piperdi

Abstract

The introduction of the epidermal growth factor receptor inhibitors (EGFR-I) has increased the treatment options available for patients with metastatic colorectal cancer (mCRC). Two EGFR-I agents currently approved for the treatment of mCRC are the fully human monoclonal antibody panitumumab and the mouse-human chimeric monoclonal antibody cetuximab. While these agents have demonstrated activity across multiple lines of therapy, early studies suggested that clinical benefit was confined to a subset of patients treated. Mutation of the KRAS oncogene has emerged as a powerful negative predictive biomarker to identify patients with mCRC who do not benefit from EGFR-I therapy. Multiple retrospective analyses have demonstrated that clinical benefit from treatment with EGFR-I is limited to patients with tumors harboring the wild-type KRAS gene. In this review, the KRAS pathway and studies evaluating KRAS as a prognostic marker in CRC are discussed along with advances in KRAS gene mutation testing. Clinical trials evaluating the role of KRAS status in response to EGFR-I monotherapy or in combination with chemotherapy are also highlighted along with ongoing studies evaluating the role of EGFR-I treatment on curative resections rates. F...Continue Reading

References

Jun 1, 1990·Cell·E R Fearon, B Vogelstein
Sep 1, 1988·The New England Journal of Medicine·B VogelsteinJ L Bos
Apr 1, 1993·Gastroenterology·J BenhattarJ Costa
Jul 8, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H BouzoureneJ C Givel
Feb 24, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M EstellerM A Peinado
Apr 6, 2001·The American Journal of Pathology·W S SamowitzM L Slattery
Jun 5, 2003·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Jul 23, 2004·The New England Journal of Medicine·David CunninghamEric Van Cutsem
Jun 1, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A RussoN Gebbia
Aug 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jantine L WestraJohn T M Plukker
Mar 30, 2006·British Journal of Cancer·C A TownsleyA M Oza
Apr 19, 2006·Cancer Research·Astrid LièvrePierre Laurent-Puig
Mar 27, 2007·Nature Reviews. Cancer·Suzanne SchubbertGideon Bollag
May 2, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemRafael G Amado
Aug 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shirin Khambata-FordDavid J Mauro
Nov 14, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·W De RoockS Tejpar
Nov 16, 2007·The New England Journal of Medicine·Derek J JonkerMalcolm J Moore
Jan 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Astrid LièvrePierre Laurent-Puig
Mar 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rafael G AmadoDavid D Chang
Aug 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marie-Christine Etienne-GrimaldiGérard Milano
Sep 20, 2008·Virchows Archiv : an International Journal of Pathology·J H J M van KriekenA Ensari
Oct 24, 2008·The New England Journal of Medicine·Christos S KarapetisJohn R Zalcberg
Nov 13, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federica Di NicolantonioAlberto Bardelli
Dec 31, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carsten BokemeyerPiotr Koralewski
Dec 31, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J Randolph HechtRafael G Amado
Feb 7, 2009·The New England Journal of Medicine·Jolien TolCornelis J A Punt
Apr 3, 2009·The New England Journal of Medicine·Eric Van CutsemPhilippe Rougier
Apr 16, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hans PrenenSabine Tejpar
Oct 7, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mariana DominguesMauricio Ostronoff
Apr 20, 2010·Diagnostic Pathology·Kelly OlinerScott D Patterson

❮ Previous
Next ❯

Citations

Dec 18, 2013·Pharmacogenomics·Jai N Patel
Mar 8, 2013·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Jennifer L HuntAlfio Ferlito
Dec 15, 2010·The Oncologist·Robert GrützmannHans D Saeger
Jan 5, 2011·Frontiers in Bioscience (Scholar Edition)·Amy R CarrollAnil K Sood
May 10, 2011·International Journal of Colorectal Disease·Jyh-Ming LiouJin-Tung Liang
Mar 27, 2012·Analytical and Bioanalytical Chemistry·Stefanie GerbigZoltan Takats
Jul 17, 2013·Expert Opinion on Therapeutic Targets·Liu HongLubi Brain
Mar 12, 2016·Clinical Colorectal Cancer·Veronica AranCarlos Gil Ferreira
Apr 14, 2012·Drug Metabolism Reviews·Jose J G MarinOscar Briz
Oct 27, 2012·Critical Reviews in Oncology/hematology·Jayshree MishraNarendra Kumar
Mar 10, 2011·International Journal of Cancer. Journal International Du Cancer·Sascha TierlingJörn Walter
Feb 15, 2011·The EMBO Journal·Kiyoshi MasudaMyriam Gorospe
Nov 18, 2015·Virchows Archiv : an International Journal of Pathology·J Han J M Van KriekenAndreas Jung
May 6, 2014·Biochimica Et Biophysica Acta·Maria-Ioanna EllinaNikos K Karamanos
Feb 24, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ondrej FialaOndrej Topolcan
Feb 19, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ting-Jing YaoPei-hua Lu
Dec 20, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jundong ZhouShuyu Zhang
Sep 29, 2011·Clinical Journal of Oncology Nursing·Jean BoucherBilal Piperdi
Aug 11, 2016·International Journal of Cancer. Journal International Du Cancer·Yayoi TakahashiHiromu Suzuki
Mar 4, 2017·Scientific Reports·Yock Ping ChowVyomesh Patel
Jan 29, 2013·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Jai N PatelHoward L McLeod
Mar 10, 2017·Journal of Clinical Gastroenterology·Min S KwakJoung I Lee
Apr 24, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Sanjay KakarYoung S Kim
Nov 11, 2010·British Journal of Cancer·T LampejoS Cleator
May 15, 2013·Oncology Reports·Thais Gulim De CarvalhoAndre Luiz Vettore
May 7, 2014·The Oncologist·Maria SchwaederleRazelle Kurzrock
Jun 30, 2010·The Oncologist·Vanessa DeschoolmeesterJan B Vermorken
Feb 6, 2016·Advances in Anatomic Pathology·Raju K PillaiScott D Patterson
Jul 24, 2020·Therapeutic Advances in Medical Oncology·Hossein TaghizadehGerald W Prager
Jul 28, 2020·Nature Communications·Léo AubertPhilippe P Roux
Sep 14, 2018·Frontiers in Molecular Biosciences·Anna P Sokolenko, Evgeny N Imyanitov

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Methods Mentioned

BETA
GTPase
PCR
surgical resection

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