Rebecca A DeStefanis1, Jeremy D Kratz1, Philip B Emmerich1, Dustin A Deming1,2,3. 1. Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison. 2. University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison. 3. McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison.
Abstract
PURPOSE OF REVIEW: Treatment options for patients with metastatic colorectal cancer continue to advance as the therapeutic implications of the molecular subtypes of this disease are becoming better understood. DNA sequencing and mismatch repair assessment are now standard of care analyses for patients with metastatic colorectal cancer Thi review describes important aspects of the biology of the clinically relevant molecular subtypes of colorectal cancer based on the current standard of care testing. In addition, the clinical treatment strategies available now and potentially in the future for these colorectal cancer subtypes are discussed. RECENT FINDINGS: Currently for metastatic colorectal cancer, standard of care molecular testing is done for mutations in exons 2, 3, and 4 of KRAS and NRAS, and BRAF V600E. Testing for mismatch repair (MMR) deficiency/microsatellite instability (MSI) status is also done. These aberrations are well known to change the clinical prognosis and guide patients' treatment strategies. Additionally, three new subtypes have emerged: PIK3CAmut, HER2 amplified, and NTRK fusions. With the addition of these emerging subtypes, tumor heterogeneity further validates the need to examine mCRC as a heterogeneous disease. Here we present recent exciting data from translational research and clinical trials exhibiting possible distinct treatment strategies for these different subtypes. SUMMARY: Altogether these data show promising treatment strategies for many of these well-known and emerging subtypes of mCRC. In addition, these also give better clinical prognostic and predictive information. We believe that as molecular testing expands PIK3CA mutation, HER2 amplification, and NTRK fusion molecular testing will be included in standard of care analyses. This incorporation of testing in clinical practice will generate further information regarding prognostic and therapeutic options for these and other CRC subtypes in the future.
PURPOSE OF REVIEW: Treatment options for patients with metastatic colorectal cancer continue to advance as the therapeutic implications of the molecular subtypes of this disease are becoming better understood. DNA sequencing and mismatch repair assessment are now standard of care analyses for patients with metastatic colorectal cancer Thi review describes important aspects of the biology of the clinically relevant molecular subtypes of colorectal cancer based on the current standard of care testing. In addition, the clinical treatment strategies available now and potentially in the future for these colorectal cancer subtypes are discussed. RECENT FINDINGS: Currently for metastatic colorectal cancer, standard of care molecular testing is done for mutations in exons 2, 3, and 4 of KRAS and NRAS, and BRAF V600E. Testing for mismatch repair (MMR) deficiency/microsatellite instability (MSI) status is also done. These aberrations are well known to change the clinical prognosis and guide patients' treatment strategies. Additionally, three new subtypes have emerged: PIK3CAmut, HER2 amplified, and NTRK fusions. With the addition of these emerging subtypes, tumor heterogeneity further validates the need to examine mCRC as a heterogeneous disease. Here we present recent exciting data from translational research and clinical trials exhibiting possible distinct treatment strategies for these different subtypes. SUMMARY: Altogether these data show promising treatment strategies for many of these well-known and emerging subtypes of mCRC. In addition, these also give better clinical prognostic and predictive information. We believe that as molecular testing expands PIK3CA mutation, HER2 amplification, and NTRK fusion molecular testing will be included in standard of care analyses. This incorporation of testing in clinical practice will generate further information regarding prognostic and therapeutic options for these and other CRC subtypes in the future.
Authors: Timothy M Pawlik; Charles R Scoggins; Daria Zorzi; Eddie K Abdalla; Axel Andres; Cathy Eng; Steven A Curley; Evelyne M Loyer; Andrea Muratore; Gilles Mentha; Lorenzo Capussotti; Jean-Nicolas Vauthey Journal: Ann Surg Date: 2005-05 Impact factor: 12.969
Authors: A de Gramont; A Figer; M Seymour; M Homerin; A Hmissi; J Cassidy; C Boni; H Cortes-Funes; A Cervantes; G Freyer; D Papamichael; N Le Bail; C Louvet; D Hendler; F de Braud; C Wilson; F Morvan; A Bonetti Journal: J Clin Oncol Date: 2000-08 Impact factor: 44.544
Authors: Astrid Lièvre; Jean-Baptiste Bachet; Delphine Le Corre; Valérie Boige; Bruno Landi; Jean-François Emile; Jean-François Côté; Gorana Tomasic; Christophe Penna; Michel Ducreux; Philippe Rougier; Frédérique Penault-Llorca; Pierre Laurent-Puig Journal: Cancer Res Date: 2006-04-15 Impact factor: 12.701
Authors: Richard M Goldberg; Daniel J Sargent; Roscoe F Morton; Charles S Fuchs; Ramesh K Ramanathan; Stephen K Williamson; Brian P Findlay; Henry C Pitot; Steven R Alberts Journal: J Clin Oncol Date: 2003-12-09 Impact factor: 44.544
Authors: David Cunningham; Yves Humblet; Salvatore Siena; David Khayat; Harry Bleiberg; Armando Santoro; Danny Bets; Matthias Mueser; Andreas Harstrick; Chris Verslype; Ian Chau; Eric Van Cutsem Journal: N Engl J Med Date: 2004-07-22 Impact factor: 91.245
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: Silvia Benvenuti; Andrea Sartore-Bianchi; Federica Di Nicolantonio; Carlo Zanon; Mauro Moroni; Silvio Veronese; Salvatore Siena; Alberto Bardelli Journal: Cancer Res Date: 2007-03-15 Impact factor: 12.701
Authors: Helen Davies; Graham R Bignell; Charles Cox; Philip Stephens; Sarah Edkins; Sheila Clegg; Jon Teague; Hayley Woffendin; Mathew J Garnett; William Bottomley; Neil Davis; Ed Dicks; Rebecca Ewing; Yvonne Floyd; Kristian Gray; Sarah Hall; Rachel Hawes; Jaime Hughes; Vivian Kosmidou; Andrew Menzies; Catherine Mould; Adrian Parker; Claire Stevens; Stephen Watt; Steven Hooper; Rebecca Wilson; Hiran Jayatilake; Barry A Gusterson; Colin Cooper; Janet Shipley; Darren Hargrave; Katherine Pritchard-Jones; Norman Maitland; Georgia Chenevix-Trench; Gregory J Riggins; Darell D Bigner; Giuseppe Palmieri; Antonio Cossu; Adrienne Flanagan; Andrew Nicholson; Judy W C Ho; Suet Y Leung; Siu T Yuen; Barbara L Weber; Hilliard F Seigler; Timothy L Darrow; Hugh Paterson; Richard Marais; Christopher J Marshall; Richard Wooster; Michael R Stratton; P Andrew Futreal Journal: Nature Date: 2002-06-09 Impact factor: 49.962
Authors: F Di Fiore; F Blanchard; F Charbonnier; F Le Pessot; A Lamy; M P Galais; L Bastit; A Killian; R Sesboüé; J J Tuech; A M Queuniet; B Paillot; J C Sabourin; F Michot; P Michel; T Frebourg Journal: Br J Cancer Date: 2007-03-20 Impact factor: 7.640
Authors: John R P Knight; Constantinos Alexandrou; George L Skalka; Nikola Vlahov; Kathryn Pennel; Leah Officer; Ana Teodosio; Georgios Kanellos; David M Gay; Sebastian May-Wilson; Ewan M Smith; Arafath K Najumudeen; Kathryn Gilroy; Rachel A Ridgway; Dustin J Flanagan; Rachael C L Smith; Laura McDonald; Craig MacKay; Anne Cheasty; Kerri McArthur; Emma Stanway; Joshua D Leach; Rene Jackstadt; Joseph A Waldron; Andrew D Campbell; Georgios Vlachogiannis; Nicola Valeri; Kevin M Haigis; Nahum Sonenberg; Christopher G Proud; Neil P Jones; Martin E Swarbrick; Heather J McKinnon; William J Faller; John Le Quesne; Joanne Edwards; Anne E Willis; Martin Bushell; Owen J Sansom Journal: Cancer Discov Date: 2020-12-16 Impact factor: 38.272
Authors: G Kazemier; R D M Steenbergen; S Bach; I Paulis; N R Sluiter; M Tibbesma; I Martin; M A van de Wiel; J B Tuynman; I Bahce Journal: Sci Rep Date: 2021-01-27 Impact factor: 4.379
Authors: P García-Alfonso; R García-Carbonero; J García-Foncillas; P Pérez-Segura; R Salazar; R Vera; S Ramón Y Cajal; J Hernández-Losa; S Landolfi; E Musulén; M Cuatrecasas; S Navarro Journal: Clin Transl Oncol Date: 2020-05-16 Impact factor: 3.405