Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies

Abstract Despite advances in metastatic colorectal cancer (mCRC) treatment, long-term survival remains poor, particularly in right-sided colorectal cancer (RCRC), which has a worse prognosis compared to left-sided CRC (LCRC). This disparity is driven by the complex biological diversity of these mali...

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Main Authors: Marwa Abdel Hamid, Lorenz M. Pammer, Silvia Oberparleiter, Michael Günther, Arno Amann, Rebecca A. Gruber, Anna Mair, Fabienne I. Nocera, Steffen Ormanns, Kai Zimmer, Romana R. Gerner, Florian Kocher, Samuel M. Vorbach, Dominik Wolf, Jakob M. Riedl, Florian Huemer, Andreas Seeber
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00892-y
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author Marwa Abdel Hamid
Lorenz M. Pammer
Silvia Oberparleiter
Michael Günther
Arno Amann
Rebecca A. Gruber
Anna Mair
Fabienne I. Nocera
Steffen Ormanns
Kai Zimmer
Romana R. Gerner
Florian Kocher
Samuel M. Vorbach
Dominik Wolf
Jakob M. Riedl
Florian Huemer
Andreas Seeber
author_facet Marwa Abdel Hamid
Lorenz M. Pammer
Silvia Oberparleiter
Michael Günther
Arno Amann
Rebecca A. Gruber
Anna Mair
Fabienne I. Nocera
Steffen Ormanns
Kai Zimmer
Romana R. Gerner
Florian Kocher
Samuel M. Vorbach
Dominik Wolf
Jakob M. Riedl
Florian Huemer
Andreas Seeber
author_sort Marwa Abdel Hamid
collection DOAJ
description Abstract Despite advances in metastatic colorectal cancer (mCRC) treatment, long-term survival remains poor, particularly in right-sided colorectal cancer (RCRC), which has a worse prognosis compared to left-sided CRC (LCRC). This disparity is driven by the complex biological diversity of these malignancies. RCRC and LCRC differ not only in clinical presentation and outcomes but also in their underlying molecular and genetic profiles. This article offers a detailed literature review focusing on the distinctions between RCRC and LCRC. We explore key differences across embryology, anatomy, pathology, omics, and the tumor microenvironment (TME), providing insights into how these factors contribute to prognosis and therapeutic responses. Furthermore, we examine the therapeutic implications of these differences, considering whether the conventional classification of CRC into right- and left-sided forms should be refined. Recent molecular findings suggest that this binary classification may overlook critical biological complexities. Therefore, we propose that future approaches should integrate molecular insights to better guide personalized treatments, especially anti-EGFR therapies, and improve patient outcomes.
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publisher Nature Portfolio
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series npj Precision Oncology
spelling doaj-art-236dd9604afc4a4cbcbc45362084d96c2025-08-20T02:19:58ZengNature Portfolionpj Precision Oncology2397-768X2025-04-019111310.1038/s41698-025-00892-yMultidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapiesMarwa Abdel Hamid0Lorenz M. Pammer1Silvia Oberparleiter2Michael Günther3Arno Amann4Rebecca A. Gruber5Anna Mair6Fabienne I. Nocera7Steffen Ormanns8Kai Zimmer9Romana R. Gerner10Florian Kocher11Samuel M. Vorbach12Dominik Wolf13Jakob M. Riedl14Florian Huemer15Andreas Seeber16Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDepartment of Gastroenterology and Hepatology, Medical University of InnsbruckDepartment of Visceral, Transplant and Thoracic Surgery, Medical University of InnsbruckINNPATH, Institute of Pathology, Tirol Kliniken GmBHDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckINNPATH, Institute of Pathology, Tirol Kliniken GmBHDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDepartment of Medicine III, Hematology and Oncology, University Hospital Rechts der Isar, Technical University of MunichDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDepartment of Radiation Oncology, Medical University of InnsbruckDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckDivision of Oncology, Department of Internal Medicine, Medical University of GrazDepartment of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical UniversityDepartment of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of InnsbruckAbstract Despite advances in metastatic colorectal cancer (mCRC) treatment, long-term survival remains poor, particularly in right-sided colorectal cancer (RCRC), which has a worse prognosis compared to left-sided CRC (LCRC). This disparity is driven by the complex biological diversity of these malignancies. RCRC and LCRC differ not only in clinical presentation and outcomes but also in their underlying molecular and genetic profiles. This article offers a detailed literature review focusing on the distinctions between RCRC and LCRC. We explore key differences across embryology, anatomy, pathology, omics, and the tumor microenvironment (TME), providing insights into how these factors contribute to prognosis and therapeutic responses. Furthermore, we examine the therapeutic implications of these differences, considering whether the conventional classification of CRC into right- and left-sided forms should be refined. Recent molecular findings suggest that this binary classification may overlook critical biological complexities. Therefore, we propose that future approaches should integrate molecular insights to better guide personalized treatments, especially anti-EGFR therapies, and improve patient outcomes.https://doi.org/10.1038/s41698-025-00892-y
spellingShingle Marwa Abdel Hamid
Lorenz M. Pammer
Silvia Oberparleiter
Michael Günther
Arno Amann
Rebecca A. Gruber
Anna Mair
Fabienne I. Nocera
Steffen Ormanns
Kai Zimmer
Romana R. Gerner
Florian Kocher
Samuel M. Vorbach
Dominik Wolf
Jakob M. Riedl
Florian Huemer
Andreas Seeber
Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies
npj Precision Oncology
title Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies
title_full Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies
title_fullStr Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies
title_full_unstemmed Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies
title_short Multidimensional differences of right- and left-sided colorectal cancer and their impact on targeted therapies
title_sort multidimensional differences of right and left sided colorectal cancer and their impact on targeted therapies
url https://doi.org/10.1038/s41698-025-00892-y
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