For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
17
views
12
references
 Top references
cited by
59
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      2,486
      similar
       All similar
      • Record: found
      • Abstract: not found
      • Article: not found

      Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches.

          Antonella De Luca, Monica Maiello, Amelia D'Alessio … (2012)
          The RAS/RAF/MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) (MAPK) and the PI3K/AKT/mammalian target of rapamycin (mTOR) (PI3K) pathways are frequently deregulated in human cancer as a result of genetic alterations in their components or upstream activation of cell-surface receptors. These signalling cascades are regulated by complex feedback and cross-talk mechanisms. In this review the key components of the MAPK and AKT pathways and their molecular alterations are described. The complex interactions between these signalling cascades are also analysed. The observation that the MAPK and the PI3K pathways are often deregulated in human cancer makes the components of these signalling cascades interesting targets for therapeutic intervention. Recently, the presence of compensatory loops that activate one pathway following the blockade of the other signalling cascade has been demonstrated. Therefore, the blockade of both pathways with combinations of signalling inhibitors might result in a more efficient anti-tumor effect as compared with a single agent. In addition, the MAPK and PI3K pathways are activated by mutations that coexist or can be mutually exclusive. In this regard, a large-scale characterization of the cancer genome might offer personalized cancer genomic information, which may improve the anti-tumor efficacy of signalling inhibitors.
          Article 0 comments Cited 235 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            Tumour heterogeneity and the evolution of polyclonal drug resistance

            Rebecca A. Burrell, Charles Swanton (2014)
            Cancer drug resistance is a major problem, with the majority of patients with metastatic disease ultimately developing multidrug resistance and succumbing to their disease. Our understanding of molecular events underpinning treatment failure has been enhanced by new genomic technologies and pre-clinical studies. Intratumour genetic heterogeneity (ITH) is a prominent contributor to therapeutic failure, and it is becoming increasingly apparent that individual tumours may achieve resistance via multiple routes simultaneously - termed polyclonal resistance. Efforts to target single resistance mechanisms to overcome therapeutic failure may therefore yield only limited success. Clinical studies with sequential analysis of tumour material are needed to enhance our understanding of inter-clonal functional relationships and tumour evolution during therapy, and to improve drug development strategies in cancer medicine.
            Article 0 comments Cited 164 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions

              A Brannon, Efsevia Vakiani, Brooke Sylvester … (2014)
              Background Colorectal cancer is the second leading cause of cancer death in the United States, with over 50,000 deaths estimated in 2014. Molecular profiling for somatic mutations that predict absence of response to anti-EGFR therapy has become standard practice in the treatment of metastatic colorectal cancer; however, the quantity and type of tissue available for testing is frequently limited. Further, the degree to which the primary tumor is a faithful representation of metastatic disease has been questioned. As next-generation sequencing technology becomes more widely available for clinical use and additional molecularly targeted agents are considered as treatment options in colorectal cancer, it is important to characterize the extent of tumor heterogeneity between primary and metastatic tumors. Results We performed deep coverage, targeted next-generation sequencing of 230 key cancer-associated genes for 69 matched primary and metastatic tumors and normal tissue. Mutation profiles were 100% concordant for KRAS, NRAS, and BRAF, and were highly concordant for recurrent alterations in colorectal cancer. Additionally, whole genome sequencing of four patient trios did not reveal any additional site-specific targetable alterations. Conclusions Colorectal cancer primary tumors and metastases exhibit high genomic concordance. As current clinical practices in colorectal cancer revolve around KRAS, NRAS, and BRAF mutation status, diagnostic sequencing of either primary or metastatic tissue as available is acceptable for most patients. Additionally, consistency between targeted sequencing and whole genome sequencing results suggests that targeted sequencing may be a suitable strategy for clinical diagnostic applications. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0454-7) contains supplementary material, which is available to authorized users.
              Article 0 comments Cited 163 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Annals of Oncology
                Abbreviated Title: Ann Oncol
                Publisher: Oxford University Press (OUP)
                ISSN (Print): 0923-7534
                ISSN (Electronic): 1569-8041
                Publication date Created: July 22 2015
                Publication date Created: August 2015
                Publication date (Print): August 2015
                Publication date (Electronic): April 07 2015
                Volume: 26
                Issue: 8
                Pages: 1710-1714
                Article
                DOI: 10.1093/annonc/mdv176
                PubMed ID: 25851630
                SO-VID: da59eaf2-049e-4996-8a6d-9bf18160945f
                Copyright © © 2015
                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content2,486

                See all similar

                Cited by57

                See all cited by