Abstract
An understanding of signaling pathways has not been fully incorporated into prognostication and therapeutic options. We evaluated the hypothesis that information about cancer-related signaling pathways can improve prognostic stratification and explain some of the clinical heterogeneity in patients with metastatic colorectal cancer. We analyzed prognostic relevance of signaling pathways in patients undergoing resection of colorectal liver metastases (CLM) from 2004-2017, and clinical actionability of gene alterations in 7 signaling pathways: p53, Wnt, RTK-RAS, PI3K, TGFβ, Notch, and cell cycle. To assess the wide applicability, the results were validated in an external retrospective cohort including patients with unresectable metastatic colorectal cancer. Of 579 patients, the numbers of patients with pathway alterations were as follows: p53, n = 420 (72.5%); Wnt, 340 (58.7%); RTK-RAS, 333 (57.5%); PI3K, 110 (19.0%); TGFβ, 65 (11.2%); Notch, 41 (7.1%); and cell cycle, 15 (2.6%). More than 80% of alterations in each pathway occurred in a single predominant gene TP53, APC, KRAS, PIK3CA, FBXW7, and RB1 in p53, Wnt, RTK-RAS, PI3K, Notch, and cell cycle pathways, respectively. Alterations of 4 pathways (p53, RTK-RAS, TGFβ, and Notch) ...Continue Reading
References
Feb 28, 1996·Statistics in Medicine·F E HarrellD B Mark
Apr 11, 2002·Cell Research·Wei Zhang, Hui Tu Liu
Aug 3, 2002·Nature Reviews. Cancer·Karen H Vousden, Xin Lu
Aug 29, 2002·Nature·Harith RajagopalanVictor E Velculescu
Jun 17, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Al B BensonDaniel G Haller
Nov 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guillaume PortierLaurent Bedenne
Oct 17, 2007·Annals of Internal Medicine·Jan P VandenbrouckeUNKNOWN STROBE initiative
Sep 2, 2008·Oncogene·P RizzoL Miele
Jul 2, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M YchouA Santoro
Aug 1, 2009·Nature Reviews. Drug Discovery·Pixu LiuJean J Zhao
Sep 5, 2009·Annals of Surgery·Yoji KishiJean-Nicolas Vauthey
Dec 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arnaud D RothFred Bosman
Jan 26, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antoine BrouquetJean-Nicolas Vauthey
Apr 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemFortunato Ciardiello
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Joan Massagué
Mar 5, 2013·Cancer Discovery·Eduardo Vilar, Josep Tabernero
Jul 3, 2013·The Journal of Molecular Diagnostics : JMD·Rajesh R SinghRajyalakshmi Luthra
Sep 11, 2013·Annals of Surgery·Jean-Nicolas VautheyDipen M Maru
Sep 18, 2014·Annals of Surgical Oncology·Yoshihiro MiseJean-Nicolas Vauthey
Jul 30, 2015·Clinical and Translational Medicine·Haiyun WangFan Zhang
Sep 13, 2016·Oncogene·T ZhanM Boutros
Nov 7, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew G SummersJeremy P Cheadle
Nov 29, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jonathan M LoreeScott Kopetz
Jan 10, 2018·Cancer Cell·Rona YaegerNikolaus Schultz
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 3, 2019·Journal of Surgical Oncology·Yoshikuni KawaguchiJean-Nicolas Vauthey
May 6, 2019·Journal of the American College of Surgeons·Yoshikuni KawaguchiJean-Nicolas Vauthey
Jun 9, 2019·Trends in Cancer·Erik S KnudsenDavid W Goodrich
Jun 22, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoshikuni KawaguchiJean-Nicolas Vauthey
Nov 6, 2020·Journal of the National Comprehensive Cancer Network : JNCCN·Yoshikuni KawaguchiJean-Nicolas Vauthey
Apr 9, 2021·The British Journal of Surgery·Y KawaguchiJ-N Vauthey