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RAS genes in colorectal carcinoma: pathogenesis, testing guidelines and treatment implications
  1. Omer Saeed1,
  2. Antonio Lopez-Beltran2,
  3. Kurt W Fisher3,
  4. Marina Scarpelli4,
  5. Rodolfo Montironi4,
  6. Alessia Cimadamore4,
  7. Francesco Massari5,
  8. Matteo Santoni6,
  9. Liang Cheng1
  1. 1 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA
  2. 2 Department of Pathology and Surgery, Faculty of Medicine, Cordoba, Spain
  3. 3 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA
  4. 4 Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
  5. 5 Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
  6. 6 Oncology Unit, Macerata Hospital, Macerata, Italy
  1. Correspondence to Dr Liang Cheng, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; liang_cheng{at}yahoo.com

Abstract

The RAS family is among the most commonly mutated genes in all human malignancies including colon cancer. In normal cells, RAS proteins act as a link in the intracellular signal transduction initiated by binding of growth factors to cell membrane receptors mediating cell survival. RAS isoproteins have great morphological similarities, but despite that, they are thought to have different functions in different tissues. RAS mutations, as supported by several studies including animal models, have a role in the development and progression of colorectal cancer. The detection of RAS mutations in patients with colorectal carcinoma, specifically KRAS and NRAS, has significant clinical implications. It is currently recommended that patients with colon cancer who are considered for antiepidermal growth factor receptor monoclonal antibodies, get RAS mutation testing since only those with wildtype-RAS genes benefit from such treatment. Despite decades of research, there is currently no effective and safe treatment that directly targets RAS-mutated neoplasms. Multiple therapeutic approaches directed against RAS mutations are currently experimental, including a promising immunotherapy study using T-cells in patients with metastatic colon cancer.

  • colorectal cancer
  • molecular diagnostics
  • personalized medicine
  • kras
  • nras
  • microsatellite instability (msi)
  • braf

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Footnotes

  • Handling editor Des Richardson.

  • Correction notice This paper has been corrected since it was published Online First. Figure 2 and 3 legends were accidentally switched and this has now been rectified.

  • Contributors OS drafted the article. LC formulated and designed the topic of this review. All the authors critically read, edited and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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