Significance of KRAS Gene Mutations in Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 25 January 2025 | Viewed by 3987

Special Issue Editors


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Guest Editor
Institute of Biomolecular Chemistry (ICB), Sassari, Italy
Interests: cancer genetics; translational medicine; molecular diagnostics

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Guest Editor
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche (CNR), 07100 Sassari, Italy
Interests: molecular profile of gastrointestinal stromal tumors (GIST); clinical cancer genomic profiling; translational medicine; molecular genetics; cancer; solid tumor; molecular biomarkers; NGS technologies
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Special Issue Information

Dear Colleagues,

Understanding biological and genetic factors is critical for therapeutic strategies and improved survival outcomes.

One of these critical steps is understanding the mechanism and development of treatment targets for metastatic colorectal cancers with the KRAS mutation.

Notably, KRAS mutations occur in many cancers with different mutation frequencies, but there is also considerable variation in mutation subtypes.

Nonetheless, the future of KRAS-directed therapy is promising.

The data require increasingly more effort to seek a better understanding to overcome what has been an un-druggable target in oncology for a long time.

The purpose of this Special Issue is to present advances regarding the heterogeneity of KRAS mutant tumors and multiple subtypes of KRAS mutant forms. Precise selection of patients for cancer-directed therapy will be necessary to ensure its efficacy.

This Special Issue welcomes reviews, as well as original research articles, which should be submitted by the deadline of 25 January 2024.

Prof. Dr. Grazia Palomba
Dr. Maria Cristina Sini
Guest Editors

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Keywords

  • KRAS
  • colorectal cancer
  • target therapy
  • mechanism
  • treatment targets

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Published Papers (2 papers)

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Research

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10 pages, 519 KiB  
Article
Determination of the Prevalence of Microsatellite Instability, BRAF and KRAS/NRAS Mutation Status in Patients with Colorectal Cancer in Slovakia
by Tomas Rendek, Rami Saade, Ondrej Pos, Georgina Kolnikova, Monika Urbanova, Jaroslav Budis, Luboslav Mihok, Miroslav Tomas, Tomas Szemes and Vanda Repiska
Cancers 2024, 16(6), 1128; https://doi.org/10.3390/cancers16061128 - 12 Mar 2024
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Abstract
Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease [...] Read more.
Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease imposes, data on molecular analysis of biomarkers in CRC-diagnosed patients is scarce. In our study, we analyzed confirmed CRC patients from the database of the National Cancer Institute (NCI) and evaluated the presence of 4 biomarkers in tumor tissues. Altogether, 83 FFPE tumor tissues from CRC patients listed in the NCI database were analyzed for microsatellite instability status, presence of BRAF and KRAS/NRAS mutations, and neoplastic cell percentage in tissue samples. We identified 4 MSI-high samples, 39 KRAS/NRAS mutations, and 5 BRAF p.V600E mutations, with one case of coexistence of all three markers in a single tumor sample. We also evaluated possible relationships between biomarkers, their coexistence, and the age and sex of the studied population. Full article
(This article belongs to the Special Issue Significance of KRAS Gene Mutations in Colorectal Cancer)
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Review

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16 pages, 1818 KiB  
Review
KRAS, a New Target for Precision Medicine in Colorectal Cancer?
by Alice Boilève, Cristina Smolenschi, Aurélien Lambert, Valérie Boige, Matthieu Delaye, Géraldine M. Camilleri, Anthony Tarabay, Marine Valéry, Alina Fuerea, Thomas Pudlarz, Jacques R. R. Mathieu, Fanny Jaulin, Antoine Hollebecque and Michel Ducreux
Cancers 2024, 16(20), 3455; https://doi.org/10.3390/cancers16203455 - 12 Oct 2024
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Abstract
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with significant public health concerns. This review examines the landscape of KRAS inhibition in colorectal cancer (CRC), focusing on recent advances in therapeutic strategies targeting this oncogene. Historically deemed undruggable due to [...] Read more.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with significant public health concerns. This review examines the landscape of KRAS inhibition in colorectal cancer (CRC), focusing on recent advances in therapeutic strategies targeting this oncogene. Historically deemed undruggable due to its complex structure and essential role in tumorigenesis, KRAS mutations are prevalent in CRC and are associated with poor prognosis. However, breakthroughs in drug development have led to the emergence of KRAS inhibitors as promising treatment options. This review discusses various classes of KRAS inhibitors, including covalent and non-covalent inhibitors, as well as combination therapies aimed at enhancing efficacy and overcoming resistance mechanisms. It highlights recent clinical trials evaluating the efficacy of KRAS inhibitors either as monotherapy or in combination with other agents, such as anti-EGFR antibodies. Despite challenges such as resistance mechanisms and tumor heterogeneity, the development of KRAS inhibitors represents a significant advance in CRC treatment and holds promise for improving patient outcomes in the future. Full article
(This article belongs to the Special Issue Significance of KRAS Gene Mutations in Colorectal Cancer)
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