Current role of antibody therapy in patients with metastatic colorectal cancer

Pfeiffer, Per; Qvortrup, Camilla; Eriksen, Jesper Grau

doi:10.1038/sj.onc.1210377

Cited by 44 publications

(47 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since heightened Wnt/b-catenin activation seems to encompass primary WT cells from our entire cohort, although in different ways, from a practical viewpoint, our results suggest that antibody therapy directed against FZD7 with or without Wnt pathway antagonists, may present future treatment options of WT, possibly in combination with chemotherapy (Barker and Clevers, 2006;Pfeiffer et al, 2007). As Ab therapy requires the presence of FZD7 on the cell surface, the observed FZD7 internalization might limit this option and call for additional forms of Wnt pathway inhibition.…”

Section: Fzd7mentioning

confidence: 99%

Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target

et al. 2011

View full text Add to dashboard Cite

Wilms' tumor (WT), the most frequent renal solid tumor in children, has been linked to aberrant Wnt signaling. Herein, we demonstrate that different WTs can be grouped according to either sensitivity or resistance to an antibody (Ab) specific to frizzled7 (FZD7), a Wnt receptor. In the FZD7-sensitive WT phenotype, the Ab induced cell death of the FZD7 þ fraction, which in turn depleted primary WT cultures of their clonogenic and sphere-forming cells and decreased in vivo proliferation and survival on xenografting to the chick chorio-allantoic-membrane. In contrast, FZD7-resistant WT in which no cell death was induced showed a different intracellular route of the Ab-FZD7 complex compared with sensitive tumors and accumulation of b-catenin. This coincided with a low sFRP1 and DKK1 (Wnt inhibitors) expression pattern, restored epigenetically with de-methylating agents, and lack of b-catenin or WTX mutations. The addition of exogenous DKK1 and sFRP1 to the tumor cells enabled the sensitization of FZD7-resistant WT to the FZD7 Ab. Finally, although extremely difficult to achieve because of dynamic cellular localization of FZD7, sorting of FZD7 þ cells from resistant WT, showed them to be highly clonogenic/proliferative, overexpressing WT 'stemness' genes, emphasizing the importance of targeting this fraction. FZD7 Ab therapy alone or in combination with Wnt pathway antagonists may have a significant role in the treatment of WT via targeting of a tumor progenitor population.

show abstract

Section: Fzd7mentioning

confidence: 99%

Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The standard advanced colorectal cancer treatment is based on the administration of fluoropyrimidines (5-fluorouracil or capecitabine) combined with oxaliplatin, the topoisomerase I inhibitor CPT-11, and the monoclonal antibodies cetuximab, bevacizumab, or panitunumab. These newer combinations have significantly improved response rates (>50%) and prolonged overall survival (2). However, drug resistance remains a major clinical challenge for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer

Martínez-Cardús

Martínez-Balibrea

Bandrés

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Oxaliplatin is a third-generation platinum agent used in colorectal cancer treatment. Oxaliplatin resistance acquisition is a complex process mainly based on alteration of genes and pathways involved in its mechanism of action. Therefore, our purpose was to perform a gene expression screening in an in vitro model to identify genes that could play a role in oxaliplatin resistance acquisition processes. Four colorectal cancer cell lines and their oxaliplatinresistant derived sublines were compared. Microarray analysis was done using Human 19K Oligo Array Slides. RNA from cells were hybridized with a commercial RNA reference sample and labeled with both fluorochromes Cy3 and Cy5. Data were analyzed by hierarchical clustering method. Subsequently, quantitative real-time PCR (qRT-PCR) was used to corroborate microarray data, considering as positively validated those genes that showed significant differences in expression levels between groups and a correlation between microarray and qRT-PCR data. By microarray analysis, 32 candidate genes were identified. After validation process by qRT-PCR, the genes AKT1, CDK5, TRIP, GARP, RGS11, and UGCGL1 were positively validated. The 3 first genes proved to be involved in regulation of nuclear factor-KB antiapoptotic transcription factor previously related to drug resistance, and the other 3 genes are novel finds. We have identified 6 genes related to oxaliplatin resistance acquisition. These findings are of paramount importance to understand these processes better and open new lines of study to elucidate the relevance of this pharmacogenomic approach into the

show abstract

“…Evidence to date suggests potentially distinct roles for bevacizumab and EGF receptor-targeted biological agents (cetuximab and panitumumab) in the treatment of metastatic CRC. Advances in adjuvant therapy have been limited to the addition of oxaliplatin and the substitution of oral fluoropyrimidine (e.g., capecitabine) with intravenous 5-fluorouracil, however there was no evidence for improved outcome with biological agents [3]. Therefore, new therapeutic options are urgently needed for advanced or metastatic CRC.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Hernanda¹,

Gonzalez²

2016

J Liver

View full text Add to dashboard Cite

Colorectal Cancer (CRC) is the third most common cancer in the world. CRC tends to metastasize to the liver, which may occur in 20% to 70% of patients and represents the major cause of death. Mesenchymal Stem/stromal cells (MSCs) have shown to be able to migrate to CRC site and play an important role in tumor progression. We have previously identified a resident MSC population in the liver. Therefore, this study aims to investigate whether there is infiltration of MSCs into patient CRC Liver Metastasis (CRC-LM) and their potential effects on tumor cell growth. By culturing resected patient CRC-LM tissue, we observed the emerging of fibroblast-like cells. Further phenotype and functional characterization confirmed their bonafide MSCs features. In situ staining with a well-established MSCs marker showed a significant enrichment of candidate MSCs in patient CRC-LM, particularly the tumor-stromal area. Moreover, MSCs secreted trophic factors significantly increased colony formation and growth of a metastatic CRC cell line. In summary, we found infiltration and enrichment of MSCs in CRC-LM patient, which could in turn nourish tumor cells.

show abstract

Current role of antibody therapy in patients with metastatic colorectal cancer

Cited by 44 publications

References 147 publications

Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target

Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target

Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer

Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Contact Info

Product

Resources

About