Literature DB >> 33322358

Precision Medicine for the Management of Therapy Refractory Colorectal Cancer.

Hossein Taghizadeh1,2, Robert M Mader1,2, Leonhard Müllauer2,3, Friedrich Erhart4, Alexandra Kautzky-Willer5, Gerald W Prager1,2.   

Abstract

In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the molecular profiles of 60 mCRC patients. Tumor samples of the patients were analyzed using next-generation sequencing panels of mutation hotspots, microsatellite instability testing, and immunohistochemistry. All profiles were reviewed by a multidisciplinary team to provide a targeted treatment recommendation after consensus discussion. In total, we detected 166 mutations in 53 patients. The five most frequently found mutations were TP53, KRAS, APC, PIK3CA, and PTEN. In 28 cases (47% of all patients), a molecularly targeted therapy could be recommended. Eventually, 12 patients (20%) received the recommended therapy. Six patients (10%) had a clinical benefit. The median time to treatment failure was 3.1 months. Our study demonstrates the feasibility and applicability of using targeted therapies in daily clinical practice for heavily pretreated mCRC patients. This could be used as a targeted treatment option in half of the patients.

Entities:  

Keywords:  colorectal cancer; molecular oncology; molecular profiling; precision medicine; targeted therapy

Year:  2020        PMID: 33322358      PMCID: PMC7768503          DOI: 10.3390/jpm10040272

Source DB:  PubMed          Journal:  J Pers Med        ISSN: 2075-4426


  35 in total

Review 1.  Precision Oncology: Who, How, What, When, and When Not?

Authors:  Lee Schwartzberg; Edward S Kim; David Liu; Deborah Schrag
Journal:  Am Soc Clin Oncol Educ Book       Date:  2017

2.  FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors.

Authors:  Leigh Marcus; Steven J Lemery; Patricia Keegan; Richard Pazdur
Journal:  Clin Cancer Res       Date:  2019-02-20       Impact factor: 12.531

3.  KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer.

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

Review 4.  Lifestyle Modifications and Colorectal Cancer.

Authors:  Lukasz Durko; Ewa Malecka-Panas
Journal:  Curr Colorectal Cancer Rep       Date:  2014

5.  Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures.

Authors:  Sigrid S Árnadóttir; Maria Jeppesen; Philippe Lamy; Jesper B Bramsen; Iver Nordentoft; Michael Knudsen; Søren Vang; Mogens R Madsen; Ole Thastrup; Jacob Thastrup; Claus L Andersen
Journal:  Mol Oncol       Date:  2017-11-27       Impact factor: 6.603

Review 6.  Heterogeneity of colon cancer: from bench to bedside.

Authors:  Marco C Merlano; Cristina Granetto; Elena Fea; Vincenzo Ricci; Ornella Garrone
Journal:  ESMO Open       Date:  2017-08-22

7.  Biomarker concordance between primary colorectal cancer and its metastases.

Authors:  D S Bhullar; J Barriuso; S Mullamitha; M P Saunders; S T O'Dwyer; O Aziz
Journal:  EBioMedicine       Date:  2019-02-04       Impact factor: 8.143

8.  Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients.

Authors:  Kristine Ø Aasebø; Anca Dragomir; Magnus Sundström; Artur Mezheyeuski; Per-Henrik Edqvist; Geir Egil Eide; Fredrik Ponten; Per Pfeiffer; Bengt Glimelius; Halfdan Sorbye
Journal:  Cancer Med       Date:  2019-05-09       Impact factor: 4.452

9.  Colorectal cancer: molecular mutations and polymorphisms.

Authors:  Aga Syed Sameer
Journal:  Front Oncol       Date:  2013-05-13       Impact factor: 6.244

10.  Spatio-temporal tumor heterogeneity in metastatic CRC tumors: a mutational-based approach.

Authors:  Sofía Del Carmen; José María Sayagués; Oscar Bengoechea; María Fernanda Anduaga; Jose Antonio Alcazar; Ruth Gervas; Jacinto García; Alberto Orfao; Luis Muñoz Bellvis; María Eugenia Sarasquete; María Del Mar Abad
Journal:  Oncotarget       Date:  2018-09-28
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  3 in total

1.  The Screening and COnsensus Based on Practices and Evidence (SCOPE) Program Results of a Survey on Daily Practice Patterns for Patients with Metastatic Colorectal Cancer-A Swiss Perspective in the Context of an International Viewpoint.

Authors:  Alexander R Siebenhüner; Giorgia Lo Presti; Daniel Helbling; Petr Szturz; Christoforos Astaras; Yannick Buccella; Sara De Dosso
Journal:  Curr Oncol       Date:  2022-08-06       Impact factor: 3.109

Review 2.  Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment.

Authors:  Yingru Zhang; Yiyang Zhao; Qi Li; Yan Wang
Journal:  Front Immunol       Date:  2021-07-13       Impact factor: 7.561

3.  Special Issue: "Gastrointestinal Cancers and Personalized Medicine".

Authors:  Stefania Nobili; Enrico Mini
Journal:  J Pers Med       Date:  2022-02-24
  3 in total

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