Literature DB >> 23792572

Contradictory KRAS mutation test results in a patient with metastatic colon cancer: a clinical dilemma in the era of personalized medicine.

Nicholas E Lamparella1, Bikramajit S Saroya, Zhaohai Yang, Nabeel E Sarwani, Wafik S El-Deiry.   

Abstract

The KRAS oncogene is mutated in 40‒50% of colorectal cancers and confers resistance to EGFR-targeted therapy. In the clinic, agents such as cetuximab or panitumumab target the EGFR receptor for therapeutic benefit. Cetuximab was approved by the FDA in 2012 as first-line therapy for KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer, in combination with FOLFIRI (5-fluorouracil, irinotecan, leucovorin). Herein we report a case of metastatic colon cancer with conflicting testing results for the KRAS oncogene from two different reference laboratories. The discordant reports complicated the decision-making process regarding the administration of targeted anti-EGFR personalized therapy. As the second test result was wild-type from the same original pathological specimen, the patient was treated with cetuximab-containing combination chemotherapy and appeared to have a response after prior disease progression. It is unclear whether the observed response was fully due to regression of wild-type KRAS-containing tumor or any component of antibody-dependent cellular cytotoxicity to a heterogeneous tumor in this patient.

Entities:  

Keywords:  KRAS mutation; cetuximab; colon cancer; targeted therapy; tumor heterogeneity

Mesh:

Substances:

Year:  2013        PMID: 23792572      PMCID: PMC3841208          DOI: 10.4161/cbt.25095

Source DB:  PubMed          Journal:  Cancer Biol Ther        ISSN: 1538-4047            Impact factor:   4.742


  12 in total

1.  Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab.

Authors:  Wendy De Roock; Derek J Jonker; Federica Di Nicolantonio; Andrea Sartore-Bianchi; Dongsheng Tu; Salvatore Siena; Simona Lamba; Sabrina Arena; Milo Frattini; Hubert Piessevaux; Eric Van Cutsem; Chris J O'Callaghan; Shirin Khambata-Ford; John R Zalcberg; John Simes; Christos S Karapetis; Alberto Bardelli; Sabine Tejpar
Journal:  JAMA       Date:  2010-10-27       Impact factor: 56.272

2.  NCCN Clinical Practice Guidelines in Oncology: colon cancer.

Authors:  Paul F Engstrom; Juan Pablo Arnoletti; Al B Benson; Yi-Jen Chen; Michael A Choti; Harry S Cooper; Anne Covey; Raza A Dilawari; Dayna S Early; Peter C Enzinger; Marwan G Fakih; James Fleshman; Charles Fuchs; Jean L Grem; Krystyna Kiel; James A Knol; Lucille A Leong; Edward Lin; Mary F Mulcahy; Sujata Rao; David P Ryan; Leonard Saltz; David Shibata; John M Skibber; Constantinos Sofocleous; James Thomas; Alan P Venook; Christopher Willett
Journal:  J Natl Compr Canc Netw       Date:  2009-09       Impact factor: 11.908

Review 3.  Hyperactive Ras in developmental disorders and cancer.

Authors:  Suzanne Schubbert; Kevin Shannon; Gideon Bollag
Journal:  Nat Rev Cancer       Date:  2007-04       Impact factor: 60.716

4.  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.

Authors:  Eric Van Cutsem; Marc Peeters; Salvatore Siena; Yves Humblet; Alain Hendlisz; Bart Neyns; Jean-Luc Canon; Jean-Luc Van Laethem; Joan Maurel; Gary Richardson; Michael Wolf; Rafael G Amado
Journal:  J Clin Oncol       Date:  2007-05-01       Impact factor: 44.544

5.  KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.

Authors:  Astrid Lièvre; Jean-Baptiste Bachet; Valérie Boige; Anne Cayre; Delphine Le Corre; Emmanuel Buc; Marc Ychou; Olivier Bouché; Bruno Landi; Christophe Louvet; Thierry André; Fréderic Bibeau; Marie-Danièle Diebold; Philippe Rougier; Michel Ducreux; Gorana Tomasic; Jean-François Emile; Frédérique Penault-Llorca; Pierre Laurent-Puig
Journal:  J Clin Oncol       Date:  2008-01-20       Impact factor: 44.544

6.  KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial.

Authors:  Susan D Richman; Matthew T Seymour; Philip Chambers; Faye Elliott; Catherine L Daly; Angela M Meade; Graham Taylor; Jennifer H Barrett; Philip Quirke
Journal:  J Clin Oncol       Date:  2009-11-02       Impact factor: 44.544

7.  Cetuximab for the treatment of colorectal cancer.

Authors:  Derek J Jonker; Chris J O'Callaghan; Christos S Karapetis; John R Zalcberg; Dongsheng Tu; Heather-Jane Au; Scott R Berry; Marianne Krahn; Timothy Price; R John Simes; Niall C Tebbutt; Guy van Hazel; Rafal Wierzbicki; Christiane Langer; Malcolm J Moore
Journal:  N Engl J Med       Date:  2007-11-15       Impact factor: 91.245

8.  Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.

Authors:  Rafael G Amado; Michael Wolf; Marc Peeters; Eric Van Cutsem; Salvatore Siena; Daniel J Freeman; Todd Juan; Robert Sikorski; Sid Suggs; Robert Radinsky; Scott D Patterson; David D Chang
Journal:  J Clin Oncol       Date:  2008-03-03       Impact factor: 44.544

9.  Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.

Authors:  Marco Gerlinger; Andrew J Rowan; Stuart Horswell; James Larkin; David Endesfelder; Eva Gronroos; Pierre Martinez; Nicholas Matthews; Aengus Stewart; Charles Swanton; M Math; Patrick Tarpey; Ignacio Varela; Benjamin Phillimore; Sharmin Begum; Neil Q McDonald; Adam Butler; David Jones; Keiran Raine; Calli Latimer; Claudio R Santos; Mahrokh Nohadani; Aron C Eklund; Bradley Spencer-Dene; Graham Clark; Lisa Pickering; Gordon Stamp; Martin Gore; Zoltan Szallasi; Julian Downward; P Andrew Futreal
Journal:  N Engl J Med       Date:  2012-03-08       Impact factor: 91.245

Review 10.  American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy.

Authors:  Carmen J Allegra; J Milburn Jessup; Mark R Somerfield; Stanley R Hamilton; Elizabeth H Hammond; Daniel F Hayes; Pamela K McAllister; Roscoe F Morton; Richard L Schilsky
Journal:  J Clin Oncol       Date:  2009-02-02       Impact factor: 44.544

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  3 in total

Review 1.  Epigenetic Biomarkers in Colorectal Cancer.

Authors:  Mukesh Verma; Vineet Kumar
Journal:  Mol Diagn Ther       Date:  2017-04       Impact factor: 4.074

2.  Genomic profiling of patient-derived colon cancer xenograft models.

Authors:  Won-Suk Lee; Hye-Youn Kim; Jae Yeon Seok; Ho Hee Jang; Yeon Ho Park; So-Young Kim; Dong Bok Shin; Suntaek Hong
Journal:  Medicine (Baltimore)       Date:  2014-12       Impact factor: 1.889

3.  Personalizing colon cancer therapeutics: targeting old and new mechanisms of action.

Authors:  Christina Leah B Kline; Wafik S El-Deiry
Journal:  Pharmaceuticals (Basel)       Date:  2013-08-21
  3 in total

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