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Cancers
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Significance of KRAS Gene Mutations in Colorectal Cancer (2nd Edition)
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Significance of KRAS Gene Mutations in Colorectal Cancer (2nd Edition)

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

Deadline for manuscript submissions: 31 March 2026 | Viewed by 1470

Special Issue Editors

Dr. Grazia Palomba

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Guest Editor
Institute of Biomolecular Chemistry (ICB), Sassari, Italy
Interests: cancer genetics; translational medicine; molecular diagnostics
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Cristina Sini

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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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of a previous one, entitled "Significance of KRAS Gene Mutations in Colorectal Cancer" (https://www.mdpi.com/journal/cancers/special_issues/LHC4758LN2).

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 and overcome what has, for a long time, been an undruggable target in oncology.

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 31 March 2026.

Dr. Grazia Palomba
Dr. Maria Cristina Sini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

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Published Papers (2 papers)

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14 pages, 703 KB  
Article
KRAS Mutations in Colorectal Adenocarcinoma: Incidence and Association with Histological Features with Particular Reference to Gly12Asp in a Multicenter GIPAD Real-World Study
by Paola Parente, Valentina Angerilli, Federica Grillo, Maria Raffaella Ambrosio, Federica Petrelli, Jessica Gasparello, Francesca Antoci, Emanuela Pilozzi, Stefania Scarpino, Flavia Adotti, Andrea Ascione, Norman Veccia, Alessandro Caputo, Mariantonia Giobbe, Roberta Gafà, Laura Melocchi, Laura Gandolfi, Paola Parrella, Barbara Pasculli, Francesco Vasuri, Maria Cristina Macciomei, Alessandro Vanoli, Luca Saragoni, Giovanni Lanza, Luca Mastracci and Matteo Fassanadd Show full author list remove Hide full author list
Cancers 2025, 17(17), 2721; https://doi.org/10.3390/cancers17172721 - 22 Aug 2025
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Abstract
Introduction: Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer-related death worldwide. CRC is characterized by morphologic and biological heterogeneity, and molecular profiling is required to select appropriate treatment in the metastatic setting. Mutations in KRAS are [...] Read more.
Introduction: Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer-related death worldwide. CRC is characterized by morphologic and biological heterogeneity, and molecular profiling is required to select appropriate treatment in the metastatic setting. Mutations in KRAS are detected in approximately 40% of CRCs, with prognostic and predictive value, and with the most frequent being p.G12D. Nonetheless, there are few data on the morphologic features in KRAS-mutated CRCs. Materials and Methods: We retrospectively collected clinicopathological features and molecular profiles of CRCs in a multicenter cohort. Results: A total of 2816 patients from 12 centers were included. KRAS mutation was found in 47.4% of cases; Gly12Asp was detected in 23.9%, with different mutation frequencies between centers. Clinicohistological features associated with Gly12Asp mutation included younger patient age (≤70 years of age), higher prevalence in males (58.6%), NOS histotype (87.1%), low pathologic grade (73.9%), high grade budding—Bd3 (43.8%), and tumoral lympho-vascular invasion (68.9%). Conclusions: Recent data have pinpointed the prognostic and predictive value of Gly12Asp mutation, and our results contribute to understanding its biology, with particular focus on peculiar clinicopathological features. Moreover, we found significant differences in pathology reports and assays for molecular profiling in different centers, which can affect a standardized therapeutic approach in CRC. Full article
(This article belongs to the Special Issue Significance of KRAS Gene Mutations in Colorectal Cancer (2nd Edition))
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15 pages, 2187 KB  
Article
Elucidating the Role of KRAS, NRAS, and BRAF Mutations and Microsatellite Instability in Colorectal Cancer via Next-Generation Sequencing
by Marta Rada Rodríguez, Bárbara Angulo Biedma, Irene Rodríguez Pérez and Javier Azúa Romeo
Cancers 2025, 17(13), 2071; https://doi.org/10.3390/cancers17132071 - 20 Jun 2025
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Abstract
Methods: We retrospectively and cross-sectionally reviewed the cases of 648 patients with a histological diagnosis of colon adenocarcinoma. Of these, 166 had partial molecular studies, and 42 cases were selected based on the availability of the genetic markers targeted in this study. We [...] Read more.
Methods: We retrospectively and cross-sectionally reviewed the cases of 648 patients with a histological diagnosis of colon adenocarcinoma. Of these, 166 had partial molecular studies, and 42 cases were selected based on the availability of the genetic markers targeted in this study. We analyzed the frequency of mutations in these genes, as well as their correlation with microsatellite instability (MSI). Results: A high mutation rate was found in the KRAS gene (52.4%). NRAS mutations were less frequent (8.9%), whereas BRAF mutations were observed in 20.8% of cases. This allowed us to identify a patient subgroup with MSI, representing 12.1% of cases. Among the 42 patients analyzed for KRAS, NRAS, BRAF, and MSI mutations, a significant association was observed between KRAS mutations and microsatellite stability, while no association was found between NRAS mutations and MSI. BRAF mutations showed a statistically significant association with MSI (p < 0.05), with the most common mutation being c.1799T > A, p.Val600Glu. The objective of this study is to demonstrate that the NGS-based method for evaluating MSI is rigorously valid compared to the results obtained using IHC and PCR. Conclusions: Comprehensive NGS profiling from the start improves diagnostic efficiency by saving time, tissue, and costs compared to gene-by-gene analysis. It also enables better molecular characterization and facilitates tailored therapeutic strategies, particularly in identifying candidates for targeted therapy and immunotherapy. This approach supports efficient tumor classification based on using KRAS, BRAF, NTRK, ERBB2, and PIK3CA as key markers, along with MSI status. We recommend that, if initial NGS is not feasible, start with KRAS analysis, then test BRAF and MSI if no mutation is found. Full article
(This article belongs to the Special Issue Significance of KRAS Gene Mutations in Colorectal Cancer (2nd Edition))
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