Unraveling the Genetic Landscape of Colorectal Cancer: The Latest Breakthroughs and Insights

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 411

Special Issue Editor


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Guest Editor
1. IFOM ETS—The AIRC Institute of Molecular Oncology, Milan, Italy
2. VHIO—Vall d’Hebron Institute of Oncology, Barcelona, Spain
Interests: colon cancer translational research; metastatic colorectal cancer; genomic profiling; immunotherapy

Special Issue Information

Dear Colleagues,

In recent years, our understanding of the genetic landscape of colorectal cancer (CRC) has advanced significantly, leading to meaningful clinical applications. From early efforts with EGFR inhibitors to recent trials with KRASG12C inhibitors, genomic profiling has become a key driver of therapeutic decisions.

A major breakthrough has been the identification of microsatellite instability (MSI) as a predictive biomarker of response to immunotherapy, which has transformed the treatment of high-MSI CRC patients. Similarly, the recognition of KRASG12C mutations and HER2 amplifications as actionable targets has expanded treatment options for specific subgroups. Recent data from studies such as BREAKWATER further support the role of precision oncology in improving outcomes for patients with aggressive disease. However, challenges remain, for example in characterizing microsatellite-stable (MSS) tumors and developing therapies against emerging targets such as PIK3CA.

This Special Issue, titled “Unraveling the Genetic Landscape of Colorectal Cancer: The Latest Breakthroughs and Insights”, invites contributions exploring recent advances in CRC genomics and their clinical implications. Topics of interest include biomarker discovery, genomic-guided therapies, ctDNA monitoring, resistance mechanisms, clonal evolution, and immunogenomic profiling. We welcome submissions of original research articles, reviews, and communications that aim to contribute to a better understanding of CRC biology and help to shape the future of precision oncology.

Dr. Nadia Saoudi Gonzalez
Guest Editor

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Keywords

  • personalized medicine
  • target therapy
  • metastatic colorectal cancer
  • precision oncology
  • biomarker discovery

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Published Papers (1 paper)

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Review

25 pages, 1079 KB  
Review
Genomic Landscape, Targeted Therapies, and Mechanisms of Resistance in Molecularly Selected Metastatic Colorectal Cancer Patients
by Patricia Garcia Pastor, Nadia Saoudi González, Francesc Salva, Javier Ros, Iosune Baraibar, Marta Rodríguez Castells, Clara Salva de Torres, Ariadna García, Adriana Alcaraz, Caterina Vaghi, Josep Tabernero and Elena Elez
Genes 2026, 17(4), 460; https://doi.org/10.3390/genes17040460 - 15 Apr 2026
Abstract
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related mortality worldwide despite substantial therapeutic improvements over the past two decades. Advances in the understanding of colorectal tumor biology and oncogenic signaling have enabled the development of biomarker-guided therapies targeting alterations [...] Read more.
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related mortality worldwide despite substantial therapeutic improvements over the past two decades. Advances in the understanding of colorectal tumor biology and oncogenic signaling have enabled the development of biomarker-guided therapies targeting alterations in EGFR, BRAFV600E, KRAS mutations and HER2 amplifications, improving outcomes in selected patient populations. Nevertheless, the emergence of both intrinsic and acquired resistance mechanisms continues to limit the durability of these responses. Resistance to targeted therapies in mCRC arises through multiple, often convergent mechanisms, including activation of compensatory signaling pathways, pre-existing genomic heterogeneity, and therapy-driven clonal selection. The integration of molecular profiling into clinical decision-making is essential to guide treatment selection and optimize therapeutic sequencing, ultimately enabling progress in precision oncology. Advances in genomic technologies, particularly circulating tumor DNA (ctDNA) analysis, have allowed longitudinal monitoring of tumor evolution, providing important insights into the mechanisms underlying resistance to targeted therapies. The aim of this review is to summarize the genomic landscape of mCRC and discuss current targeted therapeutic strategies in molecularly defined subgroups, with a particular focus on the mechanisms driving primary and acquired resistance. Full article
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